The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer

Abaza MS, Al-Saffar A, Al-Sawan S, Al-Attiyah R (2008) c-myc antisense oligonucleotides sensitize human colorectal cancer cells to chemotherapeutic drugs. Tumour Biol 295:287–303. https://doi.org/10.1159/000156706CrossRef

Adès L, Girshova L, Doronin VA, Díez-Campelo M, Valcárcel D, Kambhampati S et al (2022) Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML. Blood Adv 617:5132–5145. https://doi.org/10.1182/bloodadvances.2022007334CrossRef

Ahmad S (2010) Platinum–DNA interactions and subsequent cellular processes controlling sensitivity to anticancer platinum complexes. Chem Biodivers 73:543–566. https://doi.org/10.1002/cbdv.200800340CrossRef

Allegra CJ, Yothers G, O’Connell MJ, Sharif S, Petrelli NJ, Lopa SH et al (2013) Bevacizumab in stage II-III colon cancer: 5-year update of the national surgical adjuvant breast and bowel project C-08 trial. J Clin Oncol 313:359–364. https://doi.org/10.1200/jco.2012.44.4711CrossRef

Amaravadi RK, Schilder RJ, Martin LP, Levin M, Graham MA, Weng DE et al (2015) A phase I study of the SMAC-mimetic birinapant in adults with refractory solid tumors or lymphoma. Mol Cancer Ther 1411:2569–2575. https://doi.org/10.1158/1535-7163.Mct-15-0475CrossRef

Ambrosini G, Seelman SL, Schwartz GK (2009) Differentiation-related gene-1 decreases Bim stability by proteasome-mediated degradation. Can Res 6915:6115–6121. https://doi.org/10.1158/0008-5472.Can-08-3024CrossRef

Anastas JN, Moon RT (2013) WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer 131:11–26. https://doi.org/10.1038/nrc3419CrossRef

André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 35023:2343–2351. https://doi.org/10.1056/NEJMoa032709CrossRef

Andreeff M, Kelly KR, Yee K, Assouline S, Strair R, Popplewell L et al (2016) Results of the phase I trial of RG7112, a small-molecule MDM2 antagonist in leukemia. Clin Cancer Res 224:868–876. https://doi.org/10.1158/1078-0432.Ccr-15-0481CrossRef

Ang XL, Wade Harper J (2005) SCF-mediated protein degradation and cell cycle control. Oncogene 2417:2860–2870. https://doi.org/10.1038/sj.onc.1208614CrossRef

Bardia A, Parton M, Kümmel S, Estévez LG, Huang CS, Cortés J et al (2018) Paclitaxel with inhibitor of apoptosis antagonist, LCL161, for localized triple-negative breast cancer, prospectively stratified by gene signature in a biomarker-driven neoadjuvant trial. J Clin Oncol. https://doi.org/10.1200/jco.2017.74.8392CrossRefPubMedPubMedCentral

Bauer S, Demetri GD, Halilovic E, Dummer R, Meille C, Tan DSW et al (2021) Pharmacokinetic-pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies. Br J Cancer 1255:687–698. https://doi.org/10.1038/s41416-021-01444-4CrossRef

Benetatos CA, Mitsuuchi Y, Burns JM, Neiman EM, Condon SM, Yu G et al (2014) Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models. Mol Cancer Ther 134:867–879. https://doi.org/10.1158/1535-7163.Mct-13-0798CrossRef

Berndsen CE, Wolberger C (2014) New insights into ubiquitin E3 ligase mechanism. Nat Struct Mol Biol 214:301–307. https://doi.org/10.1038/nsmb.2780CrossRef

Bernkopf DB, Brückner M, Hadjihannas MV, Behrens J (2019) An aggregon in conductin/axin2 regulates Wnt/β-catenin signaling and holds potential for cancer therapy. Nat Commun 101:4251. https://doi.org/10.1038/s41467-019-12203-8CrossRef

Böckelman C, Engelmann BE, Kaprio T, Hansen TF, Glimelius B (2015) Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature. Acta Oncologica (stockholm, Sweden) 541:5–16. https://doi.org/10.3109/0284186x.2014.975839CrossRef

Boos SL, Loevenich LP, Vosberg S, Engleitner T, Öllinger R, Kumbrink J et al (2022) Disease modeling on tumor organoids implicates AURKA as a therapeutic target in liver metastatic colorectal cancer. Cell Mol Gastroenterol Hepatol 132:517–540. https://doi.org/10.1016/j.jcmgh.2021.10.008CrossRef

Brenke JK, Popowicz GM, Schorpp K, Rothenaigner I, Roesner M, Meininger I et al (2018) Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity. J Biol Chem 29334:13191–13203. https://doi.org/10.1074/jbc.RA118.002649CrossRef

Brusa I, Sondo E, Pesce E, Tomati V, Gioia D, Falchi F et al (2023) Innovative strategy toward Mutant CFTR rescue in cystic fibrosis: design and synthesis of thiadiazole inhibitors of the E3 ligase RNF5. J Med Chem 6614:9797–9822. https://doi.org/10.1021/acs.jmedchem.3c00608CrossRef

Buetow L, Huang DT (2016) Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Nat Rev Mol Cell Biol 1710:626–642. https://doi.org/10.1038/nrm.2016.91CrossRef

Burris HA 3rd, Fields SM (1994) Topoisomerase I inhibitors. An overview of the camptothecin analogs. Hematol Oncol Clin North Am 82:333–355CrossRef

Cacciola NA, Calabrese C, Malapelle U, Pellino G, De Stefano A, Sepe R et al (2016) UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients. Mol Carcinog 555:793–807. https://doi.org/10.1002/mc.22322CrossRef

Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D et al (2011) A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J Med Chem 548:2714–2726. https://doi.org/10.1021/jm101505dCrossRef

Callow MG, Tran H, Phu L, Lau T, Lee J, Sandoval WN et al (2011) Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PLoS ONE 67:e22595. https://doi.org/10.1371/journal.pone.0022595CrossRef

Cao Z, Zhang R, Li J, Huang H, Zhang D, Zhang J et al (2013) X-linked inhibitor of apoptosis protein (XIAP) regulation of cyclin D1 protein expression and cancer cell anchorage-independent growth via its E3 ligase-mediated protein phosphatase 2A/c-Jun axis. J Biol Chem 28828:20238–20247. https://doi.org/10.1074/jbc.M112.448365CrossRef

Ceccarelli DF, Tang X, Pelletier B, Orlicky S, Xie W, Plantevin V et al (2011) An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell 1457:1075–1087. https://doi.org/10.1016/j.cell.2011.05.039CrossRef

Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A et al (2013) Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 1543:556–568. https://doi.org/10.1016/j.cell.2013.06.048CrossRef

Chang CW, Lee HC, Li LH, Chiang Chiau JS, Wang TE, Chuang WH et al (2020) Fecal microbiota transplantation prevents intestinal injury, upregulation of toll-like receptors, and 5-Fluorouracil/Oxaliplatin-induced toxicity in colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms21020386CrossRefPubMedPubMedCentral

Chen D, Dou QP (2010) The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention. Curr Protein Pept Sci 116:459–470. https://doi.org/10.2174/138920310791824057CrossRef

Chen Q, Xie W, Kuhn DJ, Voorhees PM, Lopez-Girona A, Mendy D et al (2008) Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood 1119:4690–4699. https://doi.org/10.1182/blood-2007-09-112904CrossRef

Chen N, Balasenthil S, Reuther J, Frayna A, Wang Y, Chandler DS et al (2013) DEAR1 is a chromosome 1p35 tumor suppressor and master regulator of TGF-β-driven epithelial-mesenchymal transition. Cancer Discov 310:1172–1189. https://doi.org/10.1158/2159-8290.Cd-12-0499CrossRef

Chen N, Kong Y, Wu Y, Gao Q, Fu J, Sun X et al (2019) CAC1 knockdown reverses drug resistance through the downregulation of P-gp and MRP-1 expression in colorectal cancer. PLoS ONE 149:e0222035. https://doi.org/10.1371/journal.pone.0222035CrossRef

Chen YF, Liu RZ, Ying WW, Yang YN, Xiang SF, Shao XJ et al (2023) Arctigenin impairs UBC12 enzyme activity and cullin neddylation to attenuate cancer cells. Acta Pharmacol Sin 443:661–669. https://doi.org/10.1038/s41401-022-00992-6CrossRef

Choi TG, Nguyen MN, Kim J, Jo YH, Jang M, Nguyen NNY et al (2018) Cyclophilin B induces chemoresistance by degrading wild-type p53 via interaction with MDM2 in colorectal cancer. J Pathol 2461:115–126. https://doi.org/10.1002/path.5107CrossRef

Ci Y, Li X, Chen M, Zhong J, North BJ, Inuzuka H et al (2018) SCF(β-TRCP) E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation. Protein Cell 910:879–889. https://doi.org/10.1007/s13238-018-0510-2CrossRef

Clijsters L, Hoencamp C, Calis JJA, Marzio A, Handgraaf SM, Cuitino MC et al (2019) Cyclin F controls cell-cycle transcriptional outputs by directing the degradation of the three activator E2Fs. Mol Cell 746:1264-1277.e1267. https://doi.org/10.1016/j.molcel.2019.04.010CrossRef

Cotton TR, Lechtenberg BC (2020) Chain reactions: molecular mechanisms of RBR ubiquitin ligases. Biochem Soc Trans 484:1737–1750. https://doi.org/10.1042/bst20200237CrossRef

Crawford N, Stott KJ, Sessler T, McCann C, McDaid W, Lees A et al (2021) Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer. Mol Cancer Ther 209:1627–1639. https://doi.org/10.1158/1535-7163.Mct-20-1050CrossRef

Cusack JC Jr, Liu R, Houston M, Abendroth K, Elliott PJ, Adams J et al (2001) Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Can Res 619:3535–3540

Dang F, Nie L, Wei W (2021) Ubiquitin signaling in cell cycle control and tumorigenesis. Cell Death Differ 282:427–438. https://doi.org/10.1038/s41418-020-00648-0CrossRef

D’Angiolella V, Donato V, Vijayakumar S, Saraf A, Florens L, Washburn MP et al (2010) SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature 4667302:138–142. https://doi.org/10.1038/nature09140CrossRef

D’Angiolella V, Donato V, Forrester FM, Jeong YT, Pellacani C, Kudo Y et al (2012) Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell 1495:1023–1034. https://doi.org/10.1016/j.cell.2012.03.043CrossRef

de Jonge M, de Weger VA, Dickson MA, Langenberg M, Le Cesne A, Wagner AJ et al (2017) A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours. Eur J Cancer 76:144–151CrossRefPubMed

Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL et al (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 1414:4491–4499. https://doi.org/10.1158/1078-0432.Ccr-08-0024CrossRef

Di Y, Jing X, Hu K, Wen X, Ye L, Zhang X et al (2023) The c-MYC-WDR43 signalling axis promotes chemoresistance and tumour growth in colorectal cancer by inhibiting p53 activity. Drug Resist Updates 66:100909. https://doi.org/10.1016/j.drup.2022.100909CrossRef

Díaz-Díaz A, Casas-Pais A, Calamia V, Castosa R, Martinez-Iglesias O, Roca-Lema D et al (2017) Proteomic analysis of the E3 ubiquitin-ligase hakai highlights a role in plasticity of the cytoskeleton dynamics and in the proteasome system. J Proteome Res 168:2773–2788. https://doi.org/10.1021/acs.jproteome.7b00046CrossRef

Ding Y, Zhang Y, Xu C, Tao QH, Chen YG (2013a) HECT domain-containing E3 ubiquitin ligase NEDD4L negatively regulates Wnt signaling by targeting dishevelled for proteasomal degradation. J Biol Chem 28812:8289–8298. https://doi.org/10.1074/jbc.M112.433185CrossRef

Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM et al (2013b) Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J Med Chem 5614:5979–5983. https://doi.org/10.1021/jm400487cCrossRef

Dominguez-Brauer C, Hao Z, Elia AJ, Fortin JM, Nechanitzky R, Brauer PM et al (2016) Mule regulates the intestinal stem cell niche via the Wnt pathway and targets EphB3 for proteasomal and lysosomal degradation. Cell Stem Cell 192:205–216. https://doi.org/10.1016/j.stem.2016.04.002CrossRef

Dongre A, Weinberg RA (2019) New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 202:69–84. https://doi.org/10.1038/s41580-018-0080-4CrossRef

Drew DA, Cao Y, Chan AT (2016) Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer 163:173–186. https://doi.org/10.1038/nrc.2016.4CrossRef

Du B, Shim JS (2016) Targeting epithelial-mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules. https://doi.org/10.3390/molecules21070965CrossRefPubMedPubMedCentral

Englinger B, Mair M, Miklos W, Pirker C, Mohr T, van Schoonhoven S et al (2017) Loss of CUL4A expression is underlying cisplatin hypersensitivity in colorectal carcinoma cells with acquired trabectedin resistance. Br J Cancer 1164:489–500. https://doi.org/10.1038/bjc.2016.449CrossRef

Fang L, Yang Z, Zhou J, Tung JY, Hsiao CD, Wang L et al (2015) Circadian clock gene CRY2 degradation is involved in chemoresistance of colorectal cancer. Mol Cancer Ther 146:1476–1487. https://doi.org/10.1158/1535-7163.Mct-15-0030CrossRef

Fang M, Wu HK, Pei Y, Zhang Y, Gao X, He Y et al (2023) E3 ligase MG53 suppresses tumor growth by degrading cyclin D1. Signal Transduct Target Ther 81:263. https://doi.org/10.1038/s41392-023-01458-9CrossRef

Flanagan L, Kehoe J, Fay J, Bacon O, Lindner AU, Kay EW et al (2015) High levels of X-linked Inhibitor-of-Apoptosis Protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer. Rad Oncol (london, England) 10:131. https://doi.org/10.1186/s13014-015-0437-1CrossRef

Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S et al (2012) Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem 559:4101–4113. https://doi.org/10.1021/jm300060kCrossRef

Fouad S, Wells OS, Hill MA, D’Angiolella V (2019) Cullin ring ubiquitin ligases (CRLs) in cancer: responses to ionizing radiation (IR) treatment. Front Physiol 10:1144. https://doi.org/10.3389/fphys.2019.01144CrossRefPubMedPubMedCentral

Fujikura T, Yasuda H, Iwakura T, Tsuji T, Anders HJ (2019) MDM2 inhibitor ameliorates cisplatin-induced nephropathy via NFκΒ signal inhibition. Pharmacol Res Perspect 71:e00450. https://doi.org/10.1002/prp2.450CrossRef

Fukuda T, Kondo Y, Nakagama H (2008) The anti-proliferative effects of the CHFR depend on the forkhead associated domain, but not E3 ligase activity mediated by ring finger domain. PLoS ONE 33:e1776. https://doi.org/10.1371/journal.pone.0001776CrossRef

Gan Y, Zhou L, Wang R, Zhang Y, Li X, Han S et al (2023) Curcumol reduces aerobic glycolysis and overcomes chemoresistance by inducing Cdh1-mediated Skp2 ubiquitination. Am J Chin Med. https://doi.org/10.1142/s0192415x23500349CrossRefPubMed

Gluck WL, Gounder MM, Frank R, Eskens F, Blay JY, Cassier PA et al (2020) Phase 1 study of the MDM2 inhibitor AMG 232 in patients with advanced P53 wild-type solid tumors or multiple myeloma. Invest New Drugs 383:831–843. https://doi.org/10.1007/s10637-019-00840-1CrossRef

Gu L, Zhang H, Liu T, Zhou S, Du Y, Xiong J et al (2016) Discovery of dual inhibitors of MDM2 and XIAP for cancer treatment. Cancer Cell 304:623–636. https://doi.org/10.1016/j.ccell.2016.08.015CrossRef

Han S, Wang R, Zhang Y, Li X, Gan Y, Gao F et al (2022) The role of ubiquitination and deubiquitination in tumor invasion and metastasis. Int J Biol Sci 186:2292–2303. https://doi.org/10.7150/ijbs.69411CrossRef

Harper JW, Schulman BA (2021) Cullin-RING ubiquitin ligase regulatory circuits: a quarter century beyond the F-Box hypothesis. Annu Rev Biochem 90:403–429. https://doi.org/10.1146/annurev-biochem-090120-013613CrossRefPubMedPubMedCentral

He T, Cui J, Wu Y, Sun X, Chen N (2019) Knockdown of TRIM66 inhibits cell proliferation, migration and invasion in colorectal cancer through JAK2/STAT3 pathway. Life Sci 235:116799. https://doi.org/10.1016/j.lfs.2019.116799CrossRefPubMed

Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, Haraguchi N et al (2009) Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clin Cancer Res 1510:3423–3432. https://doi.org/10.1158/1078-0432.Ccr-08-2822CrossRef

Hu CE, Gan J (2017) TRIM37 promotes epithelial-mesenchymal transition in colorectal cancer. Mol Med Rep 153:1057–1062. https://doi.org/10.3892/mmr.2017.6125CrossRef

Hu T, Weng S, Tang W, Xue R, Chen S, Cai G et al (2015) Overexpression of BIRC6 Is a predictor of prognosis for colorectal cancer. PLoS ONE 105:e0125281. https://doi.org/10.1371/journal.pone.0125281CrossRef

Hu JL, Wang W, Lan XL, Zeng ZC, Liang YS, Yan YR et al (2019) CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol Cancer 181:91. https://doi.org/10.1186/s12943-019-1019-xCrossRef

Hua Y, Zhu Y, Zhang J, Zhu Z, Ning Z, Chen H et al (2018) miR-122 targets X-linked inhibitor of apoptosis protein to sensitize oxaliplatin-resistant colorectal cancer cells to oxaliplatin-mediated cytotoxicity. Cellular Physiol Biochem 515:2148–2159. https://doi.org/10.1159/000495832CrossRef

Huang HL, Weng HY, Wang LQ, Yu CH, Huang QJ, Zhao PP et al (2012) Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces cell growth inhibition and apoptosis. Mol Cancer Ther 115:1155–1165. https://doi.org/10.1158/1535-7163.Mct-12-0066CrossRef

Huang WL, Luo CW, Chou CL, Yang CC, Chen TJ, Li CF et al (2020) High expression of UBE2B as a poor prognosis factor in patients with rectal cancer following chemoradiotherapy. Anticancer Res 4011:6305–6317CrossRef

Huang F, Huang Z, Wei Q, Liu G, Pu J (2023a) E3 ubiquitin ligase HECTD3 is a tumor suppressor and mediates the polyubiquitination of SLC7A11 to promote ferroptosis in colon cancer. Exp Cell Res 4301:113697. https://doi.org/10.1016/j.yexcr.2023.113697CrossRef

Huang D, Wu PE, Chen ZJ, Pang YC, Xu ZW, Tan J et al (2023b) Ethanol Extract of citrus grandis “Tomentosa” exerts anticancer effects by targeting Skp2/p27 pathway in non-small cell lung cancer. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.202300061CrossRefPubMedPubMedCentral

Humblet Y (2004) Cetuximab: an IgG(1) monoclonal antibody for the treatment of epidermal growth factor receptor-expressing tumours. Expert Opin Pharmacother 57:1621–1633. https://doi.org/10.1517/14656566.5.7.1621CrossRef

Hurwitz HI, Smith DC, Pitot HC, Brill JM, Chugh R, Rouits E et al (2015) Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study. Cancer Chemother Pharmacol 754:851–859. https://doi.org/10.1007/s00280-015-2709-8CrossRef

Husnjak K, Dikic I (2012) Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 81:291–322. https://doi.org/10.1146/annurev-biochem-051810-094654CrossRefPubMed

Infante JR, Dees EC, Olszanski AJ, Dhuria SV, Sen S, Cameron S et al (2014) Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol 3228:3103–3110. https://doi.org/10.1200/jco.2013.52.3993CrossRef

Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser RS et al (2011) SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature 4717336:104–109. https://doi.org/10.1038/nature09732CrossRef

Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M et al (2004) Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 1012:1321–1328. https://doi.org/10.1038/nm1146CrossRef

Izumi D, Ishimoto T, Miyake K, Eto T, Arima K, Kiyozumi Y et al (2017) Colorectal cancer stem cells acquire chemoresistance through the upregulation of F-Box/WD repeat-containing protein 7 and the consequent degradation of c-Myc. Stem Cells 359:2027–2036. https://doi.org/10.1002/stem.2668CrossRef

Ji L, Jiang B, Jiang X, Charlat O, Chen A, Mickanin C et al (2017) The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation. Genes Dev 319:904–915. https://doi.org/10.1101/gad.300053.117CrossRef

Jiang X, Charlat O, Zamponi R, Yang Y, Cong F (2015) Dishevelled promotes Wnt receptor degradation through recruitment of ZNRF3/RNF43 E3 ubiquitin ligases. Mol Cell 583:522–533. https://doi.org/10.1016/j.molcel.2015.03.015CrossRef

Johansson H, Isabella Tsai YC, Fantom K, Chung CW, Kümper S, Martino L et al (2019) Fragment-based covalent ligand screening enables rapid discovery of inhibitors for the RBR E3 ubiquitin ligase HOIP. J Am Chem Soc 1416:2703–2712. https://doi.org/10.1021/jacs.8b13193CrossRef

Johnston PG (2005) Stage II colorectal cancer: to treat or not to treat. Oncologist 105:332–334. https://doi.org/10.1634/theoncologist.10-5-332CrossRef

Katayama K, Noguchi K, Sugimoto Y (2013) FBXO15 regulates P-glycoprotein/ABCB1 expression through the ubiquitin–proteasome pathway in cancer cells. Cancer Sci 1046:694–702. https://doi.org/10.1111/cas.12145CrossRef

Kim ES (2004) Cetuximab as a single agent or in combination with chemotherapy in lung cancer. Clin Lung Cancer 6(Suppl 2):S80-84. https://doi.org/10.3816/clc.2004.s.019CrossRefPubMed

Kim S, Jho EH (2010) The protein stability of Axin, a negative regulator of Wnt signaling, is regulated by Smad ubiquitination regulatory factor 2 (Smurf2). J Biol Chem 28547:36420–36426. https://doi.org/10.1074/jbc.M110.137471CrossRef

Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G et al (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 2516:2198–2204. https://doi.org/10.1200/jco.2006.08.2974CrossRef

Lama R, Galster SL, Xu C, Davison LW, Chemler SR, Wang X (2022) Dual targeting of MDM4 and FTH1 by MMRi71 for induced protein degradation and p53-independent apoptosis in leukemia cells. Molecules. https://doi.org/10.3390/molecules27227665CrossRefPubMedPubMedCentral

Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 153:178–196. https://doi.org/10.1038/nrm3758CrossRef

Lee HJ, Li CF, Ruan D, Powers S, Thompson PA, Frohman MA et al (2016) The DNA damage transducer RNF8 facilitates cancer chemoresistance and progression through twist activation. Mol Cell 636:1021–1033. https://doi.org/10.1016/j.molcel.2016.08.009CrossRef

Lee B, Min JA, Nashed A, Lee SO, Yoo JC, Chi SW et al (2019) A novel mechanism of irinotecan targeting MDM2 and Bcl-xL. Biochem Biophys Res Commun 5142:518–523. https://doi.org/10.1016/j.bbrc.2019.04.009CrossRef

Li M, Zhang P (2009) The function of APC/CCdh1 in cell cycle and beyond. Cell Div 4:2. https://doi.org/10.1186/1747-1028-4-2CrossRefPubMedPubMedCentral

Li N, Lorenzi F, Kalakouti E, Normatova M, Babaei-Jadidi R, Tomlinson I et al (2015) FBXW7-mutated colorectal cancer cells exhibit aberrant expression of phosphorylated-p53 at Serine-15. Oncotarget 611:9240–9256. https://doi.org/10.18632/oncotarget.3284CrossRef

Li Z, Wang Y, Li Y, Yin W, Mo L, Qian X et al (2018) Ube2s stabilizes β-Catenin through K11-linked polyubiquitination to promote mesendoderm specification and colorectal cancer development. Cell Death Dis 95:456. https://doi.org/10.1038/s41419-018-0451-yCrossRef

Li N, Babaei-Jadidi R, Lorenzi F, Spencer-Dene B, Clarke P, Domingo E et al (2019) An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance. Oncogenesis 83:13. https://doi.org/10.1038/s41389-019-0125-3CrossRef

Li Y, Wang T, Wan Q, Wang Q, Chen Z, Gao Y et al (2022) TRAF4 maintains deubiquitination of Caveolin-1 to drive glioblastoma stemness and temozolomide resistance. Can Res 8219:3573–3587. https://doi.org/10.1158/0008-5472.Can-21-3882CrossRef

Li ASM, Kimani S, Wilson B, Noureldin M, González-Álvarez H, Mamai A et al (2023) Discovery of nanomolar DCAF1 small molecule ligands. J Med Chem 667:5041–5060. https://doi.org/10.1021/acs.jmedchem.2c02132CrossRef

Liang Q, Tang C, Tang M, Zhang Q, Gao Y, Ge Z (2019) TRIM47 is up-regulated in colorectal cancer, promoting ubiquitination and degradation of SMAD4. J Exp Clin Cancer Res 381:159. https://doi.org/10.1186/s13046-019-1143-xCrossRef

Liao Y, Yuan C, Huang M, Si W, Li D, Wu W et al (2023) AZD7762 induces CRBN dependent BAG3 degradation through ubiquitin-proteasome pathway. Anticancer Drugs. https://doi.org/10.1097/cad.0000000000001532CrossRefPubMedPubMedCentral

Liu L, Wong CC, Gong B, Yu J (2018a) Functional significance and therapeutic implication of ring-type E3 ligases in colorectal cancer. Oncogene 372:148–159. https://doi.org/10.1038/onc.2017.313CrossRef

Liu M, Zhang X, Cai J, Li Y, Luo Q, Wu H et al (2018b) Downregulation of TRIM58 expression is associated with a poor patient outcome and enhances colorectal cancer cell invasion. Oncol Rep 403:1251–1260. https://doi.org/10.3892/or.2018.6525CrossRef

Liu ML, Zang F, Zhang SJ (2019) RBCK1 contributes to chemoresistance and stemness in colorectal cancer (CRC). Biomed Pharmacotherapy 118:109250. https://doi.org/10.1016/j.biopha.2019.109250CrossRef

Ma H, Wu Z, Peng J, Li Y, Huang H, Liao Y et al (2018) Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab. Int J Cancer 14212:2578–2588. https://doi.org/10.1002/ijc.31274CrossRef

Mahammedi H, Planchat E, Pouget M, Durando X, Curé H, Guy L et al (2016) The new combination docetaxel, prednisone and curcumin in patients with castration-resistant prostate cancer: a pilot phase II study. Oncology 902:69–78. https://doi.org/10.1159/000441148CrossRef

Malek E, Abdel-Malek MA, Jagannathan S, Vad N, Karns R, Jegga AG et al (2017) Pharmacogenomics and chemical library screens reveal a novel SCF(SKP2) inhibitor that overcomes Bortezomib resistance in multiple myeloma. Leukemia 313:645–653. https://doi.org/10.1038/leu.2016.258CrossRef

Martinez-Balibrea E, Martínez-Cardús A, Ginés A, Ruiz de Porras V, Moutinho C, Layos L et al (2015) Tumor-related molecular mechanisms of oxaliplatin resistance. Mol Cancer Ther 148:1767–1776. https://doi.org/10.1158/1535-7163.Mct-14-0636CrossRef

Martinez-Iglesias O, Casas-Pais A, Castosa R, Díaz-Díaz A, Roca-Lema D, Concha Á et al (2020) Hakin-1, a new specific small-molecule inhibitor for the E3 ubiquitin-ligase Hakai, inhibits carcinoma growth and progression. Cancers. https://doi.org/10.3390/cancers12051340CrossRefPubMedPubMedCentral

Martino E, Della Volpe S, Terribile E, Benetti E, Sakaj M, Centamore A et al (2017) The long story of camptothecin: From traditional medicine to drugs. Bioorg Med Chem Lett 274:701–707. https://doi.org/10.1016/j.bmcl.2016.12.085CrossRef

Maser T, Zagorski J, Kelly S, Ostrander A, Goodyke A, Nagulapally A et al (2020) The MDM2 inhibitor CGM097 combined with the BET inhibitor OTX015 induces cell death and inhibits tumor growth in models of neuroblastoma. Cancer Med 921:8144–8158. https://doi.org/10.1002/cam4.3407CrossRef

Mastropasqua F, Marzano F, Valletti A, Aiello I, Di Tullio G, Morgano A et al (2017) TRIM8 restores p53 tumour suppressor function by blunting N-MYC activity in chemo-resistant tumours. Mol Cancer 161:67. https://doi.org/10.1186/s12943-017-0634-7CrossRef

Matt P, van Zwieten-Boot B, Calvo Rojas G, Ter Hofstede H, Garcia-Carbonero R, Camarero J et al (2011) The European Medicines Agency review of Tegafur/Gimeracil/Oteracil (Teysuno™) for the treatment of advanced gastric cancer when given in combination with cisplatin: summary of the Scientific Assessment of the Committee for medicinal products for human use (CHMP). Oncologist 1610:1451–1457. https://doi.org/10.1634/theoncologist.2011-0224CrossRef

Matthews HK, Bertoli C, de Bruin RAM (2022) Cell cycle control in cancer. Nat Rev Mol Cell Biol 231:74–88. https://doi.org/10.1038/s41580-021-00404-3CrossRef

Mavrommati I, Faedda R, Galasso G, Li J, Burdova K, Fischer R et al (2018) β-TrCP- and casein Kinase II-mediated degradation of cyclin F controls timely mitotic progression. Cell Rep 2413:3404–3412. https://doi.org/10.1016/j.celrep.2018.08.076CrossRef

Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz-Flores S et al (2018) Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from the american heart association. Circulation 1378:e30–e66. https://doi.org/10.1161/cir.0000000000000556CrossRef

Messersmith WA (2017) Systemic management of colorectal cancer. J Natl Comprehens Cancer Netw 155:699–702. https://doi.org/10.6004/jnccn.2017.0077CrossRef

Milhollen MA, Narayanan U, Soucy TA, Veiby PO, Smith PG, Amidon B (2011) Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Can Res 718:3042–3051. https://doi.org/10.1158/0008-5472.Can-10-2122CrossRef

Morawska K, Goirand F, Marceau L, Devaux M, Cueff A, Bertaut A et al (2018) 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget 914:11559–11571. https://doi.org/10.18632/oncotarget.24338CrossRef

Morreale FE, Walden H (2016) Types of ubiquitin ligases. Cell 1651:248-248.e241. https://doi.org/10.1016/j.cell.2016.03.003CrossRef

Morton CL, Wadkins RM, Danks MK, Potter PM (1999) The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase. Can Res 597:1458–1463

Mukherjee S, Saha G, Roy NS, Naiya G, Ghosh MK, Roy S (2023) A small HDM2 antagonist peptide and a USP7 inhibitor synergistically inhibit the p53-HDM2-USP7 circuit. Chem Biol Drug Des 1021:126–136. https://doi.org/10.1111/cbdd.14255CrossRef

Myant KB, Cammareri P, Hodder MC, Wills J, Von Kriegsheim A, Győrffy B et al (2017) HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation. EMBO Mol Med 92:181–197. https://doi.org/10.15252/emmm.201606684CrossRef

Naito A, Yamamoto H, Kagawa Y, Naito Y, Okuzaki D, Otani K et al (2015) RFPL4A increases the G1 population and decreases sensitivity to chemotherapy in human colorectal cancer cells. J Biol Chem 29010:6326–6337. https://doi.org/10.1074/jbc.M114.614859CrossRef

Nakajima H, Fujiwara H, Furuichi Y, Tanaka K, Shimbara N (2008) A novel small-molecule inhibitor of NF-kappaB signaling. Biochem Biophys Res Commun 3684:1007–1013. https://doi.org/10.1016/j.bbrc.2008.01.166CrossRef

Nasrullah U, Haeussler K, Biyanee A, Wittig I, Pfeilschifter J, Eberhardt W (2019) Identification of TRIM25 as a negative regulator of caspase-2 expression reveals a novel target for sensitizing colon carcinoma cells to intrinsic apoptosis. Cells. https://doi.org/10.3390/cells8121622CrossRefPubMedPubMedCentral

Nasrullah U, Stanke K, Recknagel V, Bozkurt S, Wurzel P, Gauer S et al (2023) The E3 ligase TRIM25 impairs apoptotic cell death in colon carcinoma cells via destabilization of Caspase-7 mRNA: a possible role of hnRNPH1. Cells. https://doi.org/10.3390/cells12010201CrossRefPubMedPubMedCentral

Niu B, Liu J, Lv B, Lin J, Li X, Wu C et al (2021) Interplay between transforming growth factor-β and Nur77 in dual regulations of inhibitor of differentiation 1 for colonic tumorigenesis. Nat Commun 121:2809. https://doi.org/10.1038/s41467-021-23048-5CrossRef

Oberoi-Khanuja TK, Rajalingam K (2012) IAPs as E3 ligases of Rac1: shaping the move. Small GTPases 32:131–136. https://doi.org/10.4161/sgtp.19988CrossRef

Oikawa D, Sato Y, Ohtake F, Komakura K, Hanada K, Sugawara K et al (2020) Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses. Commun Biol 31:163. https://doi.org/10.1038/s42003-020-0882-8CrossRef

Park SH, Jung EH, Kim GY, Kim BC, Lim JH, Woo CH (2015) Itch E3 ubiquitin ligase positively regulates TGF-β signaling to EMT via Smad7 ubiquitination. Mol Cells 381:20–25. https://doi.org/10.14348/molcells.2015.2120CrossRef

Park SH, Jo MJ, Kim BR, Jeong YA, Na YJ, Kim JL et al (2019) Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer. Theranostics 98:2235–2251. https://doi.org/10.7150/thno.30678CrossRef

Paschall AV, Zimmerman MA, Torres CM, Yang D, Chen MR, Li X et al (2014) Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression. BMC Cancer 14:24. https://doi.org/10.1186/1471-2407-14-24CrossRefPubMedPubMedCentral

Pei J, Xiao Y, Liu X, Hu W, Sobh A, Yuan Y et al (2023) Piperlongumine conjugates induce targeted protein degradation. Cell Chem Biol 302:203-213.e217. https://doi.org/10.1016/j.chembiol.2023.01.004CrossRef

Pelletier B, Duhamel S, Tambutet G, Jarvis S, Cléroux P, David M et al (2023) Discovery of benzodiazepine-based inhibitors of the E2 enzyme UBCH10 from a cell-based p21 degradation screen. ACS Chem Biol 185:1039–1046. https://doi.org/10.1021/acschembio.2c00909CrossRef

Proietti S, Cucina A, Dobrowolny G, D’Anselmi F, Dinicola S, Masiello MG et al (2014) Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF-7 cells. J Pineal Res 571:120–129. https://doi.org/10.1111/jpi.12150CrossRef

Psatha K, Kollipara L, Drakos E, Deligianni E, Brintakis K, Patsouris E et al (2023) Interruption of p53-MDM2 interaction by Nutlin-3a in human lymphoma cell models initiates a cell-dependent global effect on transcriptome and proteome level. Cancers. https://doi.org/10.3390/cancers15153903CrossRefPubMedPubMedCentral

Qi J, Fan L, Hussain A (2015) Implications of ubiquitin ligases in castration-resistant prostate cancer. Curr Opin Oncol 273:172–176. https://doi.org/10.1097/cco.0000000000000178CrossRef

Ravandi F, Gojo I, Patnaik MM, Minden MD, Kantarjian H, Johnson-Levonas AO et al (2016) A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML). Leuk Res 48:92–100. https://doi.org/10.1016/j.leukres.2016.07.004CrossRefPubMedPubMedCentral

Ravi R, Jain AJ, Schulick RD, Pham V, Prouser TS, Allen H et al (2004) Elimination of hepatic metastases of colon cancer cells via p53-independent cross-talk between irinotecan and Apo2 ligand/TRAIL. Can Res 6424:9105–9114. https://doi.org/10.1158/0008-5472.Can-04-2488CrossRef

Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J et al (2012) Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol 1311:1133–1140. https://doi.org/10.1016/s1470-2045(12)70474-6CrossRef

Rew Y, Sun D (2014) Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem 5715:6332–6341. https://doi.org/10.1021/jm500627sCrossRef

Ribeiro F, Alves PKN, Bechara LRG, Ferreira JCB, Labeit S, Moriscot AS (2023) Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy. Int J Mol Sci. https://doi.org/10.3390/ijms24043637CrossRefPubMedPubMedCentral

Rivory LP, Robert J (1995) Molecular, cellular, and clinical aspects of the pharmacology of 20(S)camptothecin and its derivatives. Pharmacol Ther 682:269–296. https://doi.org/10.1016/0163-7258(95)02009-8CrossRef

Roilo M, Kullmann MK, Hengst L (2018) Cold-inducible RNA-binding protein (CIRP) induces translation of the cell-cycle inhibitor p27Kip1. Nucleic Acids Res 466:3198–3210. https://doi.org/10.1093/nar/gkx1317CrossRef

Rotin D, Kumar S (2009) Physiological functions of the HECT family of ubiquitin ligases. Nat Rev Mol Cell Biol 106:398–409. https://doi.org/10.1038/nrm2690CrossRef

Sackton KL, Dimova N, Zeng X, Tian W, Zhang M, Sackton TB et al (2014) Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C. Nature 5147524:646–649. https://doi.org/10.1038/nature13660CrossRef

Saif MW, Syrigos KN, Katirtzoglou NA (2009) S-1: a promising new oral fluoropyrimidine derivative. Expert Opin Investig Drugs 183:335–348. https://doi.org/10.1517/13543780902729412CrossRef

Sakamoto H, Egashira S, Saito N, Kirisako T, Miller S, Sasaki Y et al (2015) Gliotoxin suppresses NF-κB activation by selectively inhibiting linear ubiquitin chain assembly complex (LUBAC). ACS Chem Biol 103:675–681. https://doi.org/10.1021/cb500653yCrossRef

Sanders MA, Haynes B, Nangia-Makker P, Polin LA, Shekhar MP (2017) Pharmacological targeting of RAD6 enzyme-mediated translesion synthesis overcomes resistance to platinum-based drugs. J Biol Chem 29225:10347–10363. https://doi.org/10.1074/jbc.M117.792192CrossRef

Sargent D, Sobrero A, Grothey A, O’Connell MJ, Buyse M, Andre T et al (2009) Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 276:872–877. https://doi.org/10.1200/jco.2008.19.5362CrossRef

Sawa M, Masuda M, Yamada T (2016) Targeting the Wnt signaling pathway in colorectal cancer. Expert Opin Ther Targets 204:419–429. https://doi.org/10.1517/14728222.2016.1098619CrossRef

Sekeres MA, Watts J, Radinoff A, Sangerman MA, Cerrano M, Lopez PF et al (2021) Correction to: Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AML. Leukemia 3512:3637. https://doi.org/10.1038/s41375-021-01473-1CrossRef

Sekiguchi N, Kasahara S, Miyamoto T, Kiguchi T, Ohno H, Takagi T et al (2023) Phase I dose-escalation study of milademetan in patients with relapsed or refractory acute myeloid leukemia. Int J Hematol 1171:68–77. https://doi.org/10.1007/s12185-022-03464-zCrossRef

Sharma S, Kumar P (2023) Decoding the role of MDM2 as a potential ubiquitin E3 ligase and identifying the therapeutic efficiency of alkaloids against MDM2 in combating glioblastoma. ACS Omega 85:5072–5087. https://doi.org/10.1021/acsomega.2c07904CrossRef

Shay JW, Homma N, Zhou R, Naseer MI, Chaudhary AG, Al-Qahtani M, et al., (2016) Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015, BMC genomics 6:487, doi: https://doi.org/10.1186/s12864-016-2858-0

Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF (2016) Metabolism, biochemical actions, and chemical synthesis of anticancer nucleosides, nucleotides, and base analogs. Chem Rev 11623:14379–14455. https://doi.org/10.1021/acs.chemrev.6b00209CrossRef

Shen C, Nayak A, Neitzel LR, Adams AA, Silver-Isenstadt M, Sawyer LM et al (2021) The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling. Nat Commun 121:5263. https://doi.org/10.1038/s41467-021-25634-zCrossRef

Shukla S, Ying W, Gray F, Yao Y, Simes ML, Zhao Q et al (2021) Small-molecule inhibitors targeting Polycomb repressive complex 1 RING domain. Nat Chem Biol 177:784–793. https://doi.org/10.1038/s41589-021-00815-5CrossRef

Siddiqui A, Gollavilli PN, Schwab A, Vazakidou ME, Ersan PG, Ramakrishnan M et al (2019) Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers. Cell Death Differ 2611:2223–2236. https://doi.org/10.1038/s41418-019-0289-6CrossRef

Singleton MR, Uhlmann F (2017) Separase-securin complex: a cunning way to control chromosome segregation. Nat Struct Mol Biol 244:337–339. https://doi.org/10.1038/nsmb.3393CrossRef

Sondo E, Falchi F, Caci E, Ferrera L, Giacomini E, Pesce E et al (2018) Pharmacological inhibition of the ubiquitin ligase RNF5 rescues F508del-CFTR in cystic fibrosis airway epithelia. Cell Chem Biol 257:891-905.e898. https://doi.org/10.1016/j.chembiol.2018.04.010CrossRef

Soond SM, Chantry A (2011) Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT. Oncogene 3021:2451–2462. https://doi.org/10.1038/onc.2010.617CrossRef

Srikant S, Gaudet R (2019) Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters. Nat Struct Mol Biol 269:792–801. https://doi.org/10.1038/s41594-019-0280-4CrossRef

Stein EM, DeAngelo DJ, Chromik J, Chatterjee M, Bauer S, Lin C-C et al (2022) Results from a first-in-human phase I study of siremadlin (HDM201) in patients with advanced wild-type TP53 solid tumors and acute leukemia. Clin Cancer Res 285:870–881. https://doi.org/10.1158/1078-0432.Ccr-21-1295CrossRef

Stenvang J, Kümler I, Nygård SB, Smith DH, Nielsen D, Brünner N et al (2013) Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development. Front Oncol 3:313. https://doi.org/10.3389/fonc.2013.00313CrossRefPubMedPubMedCentral

Stewart MD, Ritterhoff T, Klevit RE, Brzovic PS (2016) E2 enzymes: more than just middle men. Cell Res 264:423–440. https://doi.org/10.1038/cr.2016.35CrossRef

Stintzing S, Zhang W, Heinemann V, Neureiter D, Kemmerling R, Kirchner T et al (2015) Polymorphisms in genes involved in EGFR turnover are predictive for cetuximab efficacy in colorectal cancer. Mol Cancer Ther 1410:2374–2381. https://doi.org/10.1158/1535-7163.Mct-15-0121CrossRef

Su W, Han HH, Wang Y, Zhang B, Zhou B, Cheng Y et al (2019) The polycomb repressor complex 1 drives double-negative prostate cancer metastasis by coordinating stemness and immune suppression. Cancer Cell 362:139-155.e110. https://doi.org/10.1016/j.ccell.2019.06.009CrossRef

Sun XS, Tao Y, Le Tourneau C, Pointreau Y, Sire C, Kaminsky MC et al (2020) Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study. Lancet Oncol 219:1173–1187. https://doi.org/10.1016/s1470-2045(20)30327-2CrossRef

Sun Y, Liu Y, Ma X, Hu H (2021) The influence of cell cycle regulation on chemotherapy. Int J Mol Sci. https://doi.org/10.3390/ijms22136923CrossRefPubMedPubMedCentral

Sun Y, Sun H, Qi Y, Pan M, An N, Leng X et al (2022) Ring finger protein 6 enhances chemo-resistance by transcriptionally activating proliferating cell nuclear antigen expression and attenuating DNA damage in lung adenocarcinoma. Cancer Lett 534:215609. https://doi.org/10.1016/j.canlet.2022.215609CrossRefPubMed

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA 713:209–249

Swords RT, Erba HP, DeAngelo DJ, Bixby DL, Altman JK, Maris M et al (2015) Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study. Br J Haematol 1694:534–543. https://doi.org/10.1111/bjh.13323CrossRef

Takahashi S, Fujiwara Y, Nakano K, Shimizu T, Tomomatsu J, Koyama T et al (2021) Safety and pharmacokinetics of milademetan, a MDM2 inhibitor, in Japanese patients with solid tumors: A phase I study. Cancer Sci 1126:2361–2370. https://doi.org/10.1111/cas.14875CrossRef

Tan M, Li Y, Yang R, Xi N, Sun Y (2011) Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid. PLoS ONE 611:e27726. https://doi.org/10.1371/journal.pone.0027726CrossRef

Thirion P, Michiels S, Pignon JP, Buyse M, Braud AC, Carlson RW et al (2004) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis. J Clin Oncol 2218:3766–3775. https://doi.org/10.1200/jco.2004.03.104CrossRef

Toma-Fukai S, Shimizu T (2021) Structural diversity of ubiquitin E3 ligase. Molecules. https://doi.org/10.3390/molecules26216682CrossRefPubMedPubMedCentral

Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M et al (2013) MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models. Can Res 738:2587–2597. https://doi.org/10.1158/0008-5472.Can-12-2807CrossRef

Tsilimigras MC, Fodor A, Jobin C (2017) Carcinogenesis and therapeutics: the microbiota perspective. Nat Microbiol 2:17008. https://doi.org/10.1038/nmicrobiol.2017.8CrossRefPubMedPubMedCentral

Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D et al (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 278:1386–1422. https://doi.org/10.1093/annonc/mdw235CrossRef

van Wijk SJ, Timmers HT (2010) The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins. FASEB J 244:981–993. https://doi.org/10.1096/fj.09-136259CrossRef

Vander Heiden MG, DeBerardinis RJ (2017) Understanding the intersections between metabolism and cancer biology. Cell 1684:657–669. https://doi.org/10.1016/j.cell.2016.12.039CrossRef

Varshavsky A (2012) The ubiquitin system, an immense realm. Annu Rev Biochem 81:167–176. https://doi.org/10.1146/annurev-biochem-051910-094049CrossRefPubMed

Vassilev LT (2007) MDM2 inhibitors for cancer therapy. Trends Mol Med 131:23–31. https://doi.org/10.1016/j.molmed.2006.11.002CrossRef

Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P, Vymetalkova V (2020) 5-fluorouracil and other fluoropyrimidines in colorectal cancer: past, present and future. Pharmacol Ther 206:107447. https://doi.org/10.1016/j.pharmthera.2019.107447CrossRefPubMed

Wade M, Li YC, Wahl GM (2013) MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 132:83–96. https://doi.org/10.1038/nrc3430CrossRef

Wan J, Zhu J, Li G, Zhang Z (2016) Radiosensitization of human colorectal cancer cells by MLN4924: an inhibitor of NEDD8-activating enzyme. Technol Cancer Res Treat 154:527–534. https://doi.org/10.1177/1533034615588197CrossRef

Wang Z, Inuzuka H, Zhong J, Liu P, Sarkar FH, Sun Y et al (2012) Identification of acetylation-dependent regulatory mechanisms that govern the oncogenic functions of Skp2. Oncotarget 311:1294–1300. https://doi.org/10.18632/oncotarget.740CrossRef

Wang L, Yang H, Abel EV, Ney GM, Palmbos PL, Bednar F et al (2015) ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis. Genes Dev 292:171–183. https://doi.org/10.1101/gad.253591.114CrossRef

Wang X, De Geyter C, Jia Z, Peng Y, Zhang H (2020a) HECTD1 regulates the expression of SNAIL: Implications for epithelial-mesenchymal transition. Int J Oncol 565:1186–1198. https://doi.org/10.3892/ijo.2020.5002CrossRef

Wang S, Wang T, Wang L, Zhong L, Li K (2020b) Overexpression of RNF126 promotes the development of colorectal cancer via enhancing p53 ubiquitination and degradation. Onco Targets Ther 13:10917–10929. https://doi.org/10.2147/ott.S271855CrossRefPubMedPubMedCentral

Wang N, Yang L, Dai J, Wu Y, Zhang R, Jia X et al (2021) 5-FU inhibits migration and invasion of CRC cells through PI3K/AKT pathway regulated by MARCH1. Cell Biol Int 452:368–381. https://doi.org/10.1002/cbin.11493CrossRef

Wang H, Yang W, Qin Q, Yang X, Yang Y, Liu H et al (2022) E3 ubiquitin ligase MAGI3 degrades c-Myc and acts as a predictor for chemotherapy response in colorectal cancer. Mol Cancer 211:151. https://doi.org/10.1186/s12943-022-01622-9CrossRef

Wang Y, Gao G, Wei X, Zhang Y, Yu J (2023) UBE2T promotes temozolomide resistance of glioblastoma through regulating the Wnt/β-Catenin signaling pathway. Drug Des Dev Ther 17:1357–1369. https://doi.org/10.2147/dddt.S405450CrossRef

Weber J, Polo S, Maspero E (2019) HECT E3 ligases: a tale with multiple facets. Front Physiol 10:370. https://doi.org/10.3389/fphys.2019.00370CrossRefPubMedPubMedCentral

Wu L, Grigoryan AV, Li Y, Hao B, Pagano M, Cardozo TJ (2012) Specific small molecule inhibitors of Skp2-mediated p27 degradation. Chem Biol 1912:1515–1524. https://doi.org/10.1016/j.chembiol.2012.09.015CrossRef

Wu B, Piloto S, Zeng W, Hoverter NP, Schilling TF, Waterman ML (2013) Ring Finger Protein 14 is a new regulator of TCF/β-catenin-mediated transcription and colon cancer cell survival. EMBO Rep 144:347–355. https://doi.org/10.1038/embor.2013.19CrossRef

Wu H, Lu XX, Wang JR, Yang TY, Li XM, He XS et al (2019) TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/β-catenin degradation and is targeted for GSK3B/GSK3β-mediated phosphorylation and degradation. Autophagy 159:1506–1522. https://doi.org/10.1080/15548627.2019.1586250CrossRef

Xiao C, Wu G, Zhou Z, Zhang X, Wang Y, Song G et al (2019) RBBP6, a RING finger-domain E3 ubiquitin ligase, induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer. Cell Death Dis 1011:833. https://doi.org/10.1038/s41419-019-2070-7CrossRef

Xiong Z, Fu Z, Shi J, Jiang X, Wan H (2017) HtrA1 down-regulation induces cisplatin resistance in colon cancer by increasing XIAP and activating PI3K/Akt pathway. Ann Clin Lab Sci 473:264–270

Xu M, Zhu C, Zhao X, Chen C, Zhang H, Yuan H et al (2015) Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors. Oncotarget 62:979–994. https://doi.org/10.18632/oncotarget.2825CrossRef

Xu J, Lv G, Xu B, Jiang B (2020) Overexpression of UBE2M through Wnt/β-Catenin signaling is associated with poor prognosis and chemotherapy resistance in colorectal cancer. Trans Cancer Res 99:5614–5625. https://doi.org/10.21037/tcr-20-2641CrossRef

Xu Y, Qiu A, Peng F, Tan X, Wang J, Gong X (2021) Exosomal transfer of circular RNA FBXW7 ameliorates the chemoresistance to oxaliplatin in colorectal cancer by sponging miR-18b-5p. Neoplasma 681:108–118. https://doi.org/10.4149/neo_2020_200417N414CrossRef

Yamaguchi K, Shimamura T, Tada M (2006) [Capecitabine].Gan to kagaku ryoho. Cancer Chemotherapy 337:891–895

Yan X, Chen J, Meng Y, He C, Zou S, Li P et al (2019) RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase-9-caspase-3-dependent apoptotic pathway. Cancer Med 86:3094–3104. https://doi.org/10.1002/cam4.2203CrossRef

Yan W, Zhong Y, Hu X, Xu T, Zhang Y, Kales S et al (2023) Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes. Nat Commun 141:4798. https://doi.org/10.1038/s41467-023-40537-xCrossRef

Yang C, Wu J, He H, Liu H (2020) Small molecule NSC1892 targets the CUL4A/4B-DDB1 interactions and causes impairment of CRL4(DCAF4) E3 ligases to inhibit colorectal cancer cell growth. Int J Biol Sci 166:1059–1070. https://doi.org/10.7150/ijbs.40235CrossRef

Yu M, Tong X, Qi B, Qu H, Dong S, Yu B et al (2014) Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF-κB. Mol Med Rep 91:249–254. https://doi.org/10.3892/mmr.2013.1762CrossRef

Yu P, Fan Y, Qu X, Zhang J, Song N, Liu J et al (2016) Cbl-b regulates the sensitivity of cetuximab through ubiquitin-proteasome system in human gastric cancer cells. J BUON 214:867–873

Yu Z, Jiang X, Qin L, Deng H, Wang J, Ren W et al (2021) A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination. Oncogene 405:1027–1042. https://doi.org/10.1038/s41388-020-01572-wCrossRef

Zarkou V, Galaras A, Giakountis A, Hatzis P (2018) Crosstalk mechanisms between the WNT signaling pathway and long non-coding RNAs. Non-Coding RNA Res 32:42–53. https://doi.org/10.1016/j.ncrna.2018.04.001CrossRef

Zeng X, Sigoillot F, Gaur S, Choi S, Pfaff KL, Oh DC et al (2010) Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer Cell 184:382–395. https://doi.org/10.1016/j.ccr.2010.08.010CrossRef

Zhang S, Zhou L, Hong B, van den Heuvel AP, Prabhu VV, Warfel NA et al (2015) Small-molecule NSC59984 restores p53 pathway signaling and antitumor effects against colorectal cancer via p73 activation and degradation of mutant p53. Can Res 7518:3842–3852. https://doi.org/10.1158/0008-5472.Can-13-1079CrossRef

Zhang X, Li CF, Zhang L, Wu CY, Han L, Jin G et al (2016) TRAF6 restricts p53 mitochondrial translocation, apoptosis, and tumor suppression. Mol Cell 644:803–814. https://doi.org/10.1016/j.molcel.2016.10.002CrossRef

Zhang Y, Feng Y, Ji D, Wang Q, Qian W, Wang S et al (2018) TRIM27 functions as an oncogene by activating epithelial-mesenchymal transition and p-AKT in colorectal cancer. Int J Oncol 532:620–632. https://doi.org/10.3892/ijo.2018.4408CrossRef

Zhang Z, He G, Lv Y, Liu Y, Niu Z, Feng Q et al (2022) HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer. Cell Death Dis 131:74. https://doi.org/10.1038/s41419-022-04511-7CrossRef

Zhao CY, Szekely L, Bao W, Selivanova G (2010) Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Can Res 708:3372–3381. https://doi.org/10.1158/0008-5472.Can-09-2787CrossRef

Zhao Y, Morgan MA, Sun Y (2014) Targeting Neddylation pathways to inactivate cullin-RING ligases for anticancer therapy. Antioxid Redox Signal 2117:2383–2400. https://doi.org/10.1089/ars.2013.5795CrossRef

Zhao C, Zhao Q, Zhang C, Wang G, Yao Y, Huang X et al (2017) miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis. Sci Rep 71:4194. https://doi.org/10.1038/s41598-017-04172-zCrossRef

Zhao Z, Zhang G, Li W (2020) MT2A promotes oxaliplatin resistance in colorectal cancer cells. Cell Biochem Biophys 784:475–482. https://doi.org/10.1007/s12013-020-00930-5CrossRef

Zhao Y, Li J, Chen J, Ye M, Jin X (2022) Functional roles of E3 ubiquitin ligases in prostate cancer. J Mol Med (berl) 1008:1125–1144. https://doi.org/10.1007/s00109-022-02229-9CrossRef

Zheng S, Zhou C, Wang Y, Li H, Sun Y, Shen Z (2020) TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1. J Exp Clin Cancer Res 391:23. https://doi.org/10.1186/s13046-019-1504-5CrossRef

Zhong J, Ogura K, Wang Z, Inuzuka H (2013) Degradation of the transcription factor Twist, an oncoprotein that promotes cancer metastasis. Discov Med 1580:7–15

Zhong T, Zhang J, Liu X, Li H (2023) TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer. Cell Oncol (dordr). https://doi.org/10.1007/s13402-023-00825-6CrossRefPubMed

Zhou Q, Pham KTM, Hu H, Kurasawa Y, Li Z (2019) A kinetochore-based ATM/ATR-independent DNA damage checkpoint maintains genomic integrity in trypanosomes. Nucleic Acids Res 4715:7973–7988. https://doi.org/10.1093/nar/gkz476CrossRef

Zhou L, Yu X, Li M, Gong G, Liu W, Li T et al (2020) Cdh1-mediated Skp2 degradation by dioscin reprogrammes aerobic glycolysis and inhibits colorectal cancer cells growth. EBioMedicine 51:102570. https://doi.org/10.1016/j.ebiom.2019.11.031CrossRefPubMed

Zhou S, Peng J, Xiao L, Zhou C, Fang Y, Ou Q et al (2021a) TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability. Cell Death Dis 125:463. https://doi.org/10.1038/s41419-021-03734-4CrossRef

Zhou G, Wu H, Lin J, Lin R, Feng B, Liu Z (2021b) TRIM21 Is decreased in colitis-associated cancer and negatively regulates epithelial carcinogenesis. Inflamm Bowel Dis 274:458–468. https://doi.org/10.1093/ibd/izaa229CrossRef

Zhu GX, Gao D, Shao ZZ, Chen L, Ding WJ, Yu QF (2021a) Wnt/β-catenin signaling: Causes and treatment targets of drug resistance in colorectal cancer (Review). Mol Med Rep. https://doi.org/10.3892/mmr.2020.11744CrossRefPubMedPubMedCentral

Zhu L, Wu J, Liu H (2021b) Downregulation of HERC5 E3 ligase attenuates the ubiquitination of CtBP1 to inhibit apoptosis in colorectal cancer cells. Carcinogenesis 428:1119–1130. https://doi.org/10.1093/carcin/bgab053CrossRef

Zhuang J, Shirazi F, Singh RK, Kuiatse I, Wang H, Lee HC et al (2019) Ubiquitin-activating enzyme inhibition induces an unfolded protein response and overcomes drug resistance in myeloma. Blood 13314:1572–1584. https://doi.org/10.1182/blood-2018-06-859686CrossRef

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer

Abstract

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2024

Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma

Predicting pathological complete response to neoadjuvant chemotherapy in breast cancer patients: use of MRI radiomics data from three regions with multiple machine learning algorithms

Resveratrol ameliorates glioblastoma inflammatory response by reducing NLRP3 inflammasome activation through inhibition of the JAK2/STAT3 pathway

Alteration of serum bile acid profiles of HBV-related hepatocellular carcinoma identified by LC–MS/MS

Development of a nomogram to predict the prognosis of patients with secondary bone tumors in the intensive care unit: a retrospective analysis based on the MIMIC IV database

Transcriptome analysis reveals the clinical significance of CXCL13 in Pan-Gyn tumors

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials