Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Metastasis | Review

Intracellular and extracellular factors of colorectal cancer liver metastasis: a pivotal perplex to be fully elucidated

Authors: Yaru Niu, Wenwei Yang, Haili Qian, Yongkun Sun

Published in: Cancer Cell International | Issue 1/2022

Login to get access

Abstract

Metastasis is the leading cause of death in colorectal cancer (CRC) patients, and the liver is the most common site of metastasis. Tumor cell metastasis can be thought of as an invasion-metastasis cascade and metastatic organotropism is thought to be a process that relies on the intrinsic properties of tumor cells and their interactions with molecules and cells in the microenvironment. Many studies have provided new insights into the molecular mechanism and contributing factors involved in CRC liver metastasis for a better understanding of the organ-specific metastasis process. The purpose of this review is to summarize the theories that explain CRC liver metastasis at multiple molecular dimensions (including genetic and non-genetic factors), as well as the main factors that cause CRC liver metastasis. Many findings suggest that metastasis may occur earlier than expected and with specific organ-anchoring property. The emergence of potential metastatic clones, the timing of dissemination, and the distinct routes of metastasis have been explained by genomic studies. The main force of CRC liver metastasis is also thought to be epigenetic alterations and dynamic phenotypic traits. Furthermore, we review key extrinsic factors that influence CRC cell metastasis and liver tropisms, such as pre-niches, tumor stromal cells, adhesion molecules, and immune/inflammatory responses in the tumor microenvironment. In addition, biomarkers associated with early diagnosis, prognosis, and recurrence of liver metastasis from CRC are summarized to enlighten potential clinical practice, including some markers that can be used as therapeutic targets to provide new perspectives for the treatment strategies of CRC liver metastasis.
Literature
1.
2.
Sawatzki M, Guller U, Gusewell S, Husarik DB, Semela D, Brand S. Contrast-enhanced ultrasound can guide the therapeutic strategy by improving the detection of colorectal liver metastases. J Hepatol. 2021;74(2):419–27.PubMedCrossRef
3.
Tamas K, Walenkamp AM, de Vries EG, van Vugt MA, Beets-Tan RG, van Etten B, de Groot DJ, Hospers GA. Rectal and colon cancer: not just a different anatomic site. Cancer Treat Rev. 2015;41(8):671–9.PubMedCrossRef
4.
Zarour LR, Anand S, Billingsley KG, Bisson WH, Cercek A, Clarke MF, Coussens LM, Gast CE, Geltzeiler CB, Hansen L, et al. Colorectal cancer liver metastasis: evolving paradigms and future directions. Cell Mol Gastroenterol Hepatol. 2017;3(2):163–73.PubMedPubMedCentralCrossRef
5.
6.
Cherradi S, Ayrolles-Torro A, Vezzo-Vie N, Gueguinou N, Denis V, Combes E, Boissiere F, Busson M, Canterel-Thouennon L, Mollevi C, et al. Antibody targeting of claudin-1 as a potential colorectal cancer therapy. J Exp Clin Cancer Res. 2017;36(1):89.PubMedPubMedCentralCrossRef
7.
8.
Urosevic J, Garcia-Albeniz X, Planet E, Real S, Cespedes MV, Guiu M, Fernandez E, Bellmunt A, Gawrzak S, Pavlovic M, et al. Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH. Nat Cell Biol. 2014;16(7):685–94.PubMedCrossRef
9.
Langley RR, Fidler IJ. The seed and soil hypothesis revisited–the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer. 2011;128(11):2527–35.PubMedPubMedCentralCrossRef
10.
Lin Q, Ren L, Jian M, Xu P, Li J, Zheng P, Feng Q, Yang L, Ji M, Wei Y, et al. The mechanism of the premetastatic niche facilitating colorectal cancer liver metastasis generated from myeloid-derived suppressor cells induced by the S1PR1-STAT3 signaling pathway. Cell Death Dis. 2019;10(10):693.PubMedPubMedCentralCrossRef
11.
Wang M, Su Z, Amoah Barnie P. Crosstalk among colon cancer-derived exosomes, fibroblast-derived exosomes, and macrophage phenotypes in colon cancer metastasis. Int Immunopharmacol. 2020;81: 106298.PubMedCrossRef
12.
Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331(6024):1559–64.PubMedCrossRef
13.
14.
15.
16.
Bhattacharya R, Panda CK, Nandi S, Mukhopadhyay A. An insight into metastasis: random or evolving paradigms? Pathol Res Pract. 2018;214(8):1064–73.PubMedCrossRef
17.
Zheng W, Wu F, Fu K, Sun G, Sun G, Li X, Jiang W, Cao H, Wang H, Tang W. Emerging mechanisms and treatment progress on liver metastasis of colorectal cancer. Onco Targets Ther. 2021;14:3013–36.PubMedPubMedCentralCrossRef
18.
Weidle UH, Birzele F, Kruger A. Molecular targets and pathways involved in liver metastasis of colorectal cancer. Clin Exp Metastasis. 2015;32(6):623–35.PubMedCrossRef
19.
20.
Budczies J, von Winterfeld M, Klauschen F, Bockmayr M, Lennerz JK, Denkert C, Wolf T, Warth A, Dietel M, Anagnostopoulos I, et al. The landscape of metastatic progression patterns across major human cancers. Oncotarget. 2015;6(1):570–83.PubMedCrossRef
21.
22.
Klein CA. Selection and adaptation during metastatic cancer progression. Nature. 2013;501(7467):365–72.PubMedCrossRef
23.
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–35.PubMedPubMedCentralCrossRef
24.
Yang L, Li T, Shi H, Zhou Z, Huang Z, Lei X. The cellular and molecular components involved in pre-metastatic niche formation in colorectal cancer liver metastasis. Expert Rev Gastroenterol Hepatol. 2021;15(4):389–99.PubMedCrossRef
25.
Li C, Pan B, Liu X, Qin J, Wang X, He B, Pan Y, Sun H, Xu T, Xu X, et al. Long intergenic non-coding RNA LINC00485 exerts tumor-suppressive activity by regulating miR-581/EDEM1 axis in colorectal cancer. Aging. 2021;13(3):3866–85.PubMedPubMedCentralCrossRef
26.
Zhou H, Liu Z, Wang Y, Wen X, Amador EH, Yuan L, Ran X, Xiong L, Ran Y, Chen W, et al. Colorectal liver metastasis: molecular mechanism and interventional therapy. Signal Transduct Target Ther. 2022;7(1):70.PubMedPubMedCentralCrossRef
27.
Zhao S, Mi Y, Guan B, Zheng B, Wei P, Gu Y, Zhang Z, Cai S, Xu Y, Li X, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol. 2020;13(1):156.PubMedPubMedCentralCrossRef
28.
Wang D, Sun H, Wei J, Cen B, DuBois RN. CXCL1 Is critical for premetastatic niche formation and metastasis in colorectal cancer. Cancer Res. 2017;77(13):3655–65.PubMedPubMedCentralCrossRef
29.
Jiang K, Chen H, Fang Y, Chen L, Zhong C, Bu T, Dai S, Pan X, Fu D, Qian Y, et al. Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness. J Exp Clin Cancer Res. 2021;40(1):21.PubMedPubMedCentralCrossRef
30.
Sun H, Meng Q, Shi C, Yang H, Li X, Wu S, Familiari G, Relucenti M, Aschner M, Wang X, et al. Hypoxia-inducible exosomes facilitate liver-tropic premetastatic niche in colorectal cancer. Hepatology. 2021;74(5):2633–51.PubMedCrossRef
31.
Shao S, Zhu Y, Meng T, Liu Y, Hong Y, Yuan M, Yuan H, Hu F. Targeting high expressed alpha5beta1 integrin in liver metastatic lesions to resist metastasis of colorectal cancer by rpm peptide-modified chitosan-stearic micelles. Mol Pharm. 2018;15(4):1653–63.PubMedCrossRef
32.
Ganesh K, Basnet H, Kaygusuz Y, Laughney AM, He L, Sharma R, O’Rourke KP, Reuter VP, Huang YH, Turkekul M, et al. L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer. Nat Cancer. 2020;1(1):28–45.PubMedPubMedCentralCrossRef
33.
Patel SA, Rodrigues P, Wesolowski L, Vanharanta S. Genomic control of metastasis. Br J Cancer. 2021;124(1):3–12.PubMedCrossRef
34.
Kim TM, Jung SH, An CH, Lee SH, Baek IP, Kim MS, Park SW, Rhee JK, Lee SH, Chung YJ. Subclonal genomic architectures of primary and metastatic colorectal cancer based on intratumoral genetic heterogeneity. Clin Cancer Res. 2015;21(19):4461–72.PubMedCrossRef
35.
Saito T, Niida A, Uchi R, Hirata H, Komatsu H, Sakimura S, Hayashi S, Nambara S, Kuroda Y, Ito S, et al. A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer. Nat Commun. 2018;9(1):2884.PubMedPubMedCentralCrossRef
36.
37.
Leung ML, Davis A, Gao R, Casasent A, Wang Y, Sei E, Vilar E, Maru D, Kopetz S, Navin NE. Single-cell DNA sequencing reveals a late-dissemination model in metastatic colorectal cancer. Genome Res. 2017;27(8):1287–99.PubMedPubMedCentralCrossRef
38.
Chen HN, Shu Y, Liao F, Liao X, Zhang H, Qin Y, Wang Z, Luo M, Liu Q, Xue Z, et al. Genomic evolution and diverse models of systemic metastases in colorectal cancer. Gut. 2022;71(2):322–32.PubMedCrossRef
39.
40.
Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008;135(4):1079–99.PubMedCrossRef
41.
42.
Alderton GK. Tumour evolution: epigenetic and genetic heterogeneity in metastasis. Nat Rev Cancer. 2017;17(3):141.PubMedCrossRef
43.
Vignot S, Lefebvre C, Frampton GM, Meurice G, Yelensky R, Palmer G, Capron F, Lazar V, Hannoun L, Miller VA, et al. Comparative analysis of primary tumour and matched metastases in colorectal cancer patients: evaluation of concordance between genomic and transcriptional profiles. Eur J Cancer. 2015;51(7):791–9.PubMedCrossRef
44.
Priestley P, Baber J, Lolkema MP, Steeghs N, de Bruijn E, Shale C, Duyvesteyn K, Haidari S, van Hoeck A, Onstenk W, et al. Pan-cancer whole-genome analyses of metastatic solid tumours. Nature. 2019;575(7781):210–6.PubMedPubMedCentralCrossRef
45.
Nguyen B, Fong C, Luthra A, Smith SA, DiNatale RG, Nandakumar S, Walch H, Chatila WK, Madupuri R, Kundra R, et al. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell. 2022;185(3):563–75.PubMedCrossRef
46.
Joung JG, Oh BY, Hong HK, Al-Khalidi H, Al-Alem F, Lee HO, Bae JS, Kim J, Cha HU, Alotaibi M, et al. Tumor heterogeneity predicts metastatic potential in colorectal cancer. Clin Cancer Res. 2017;23(23):7209–16.PubMedCrossRef
47.
Sottoriva A, Barnes CP, Graham TA. Catch my drift? Making sense of genomic intra-tumour heterogeneity. Biochim Biophys Acta Rev Cancer. 2017;1867(2):95–100.PubMedCrossRef
48.
Loeb LA, Kohrn BF, Loubet-Senear KJ, Dunn YJ, Ahn EH, O’Sullivan JN, Salk JJ, Bronner MP, Beckman RA. Extensive subclonal mutational diversity in human colorectal cancer and its significance. Proc Natl Acad Sci USA. 2019;116(52):26863–72.PubMedCentralCrossRef
49.
Oga T, Yamashita Y, Soda M, Kojima S, Ueno T, Kawazu M, Suzuki N, Nagano H, Hazama S, Izumiya M, et al. Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes. Cancer Sci. 2019;110(9):2973–81.PubMedPubMedCentralCrossRef
50.
Li C, Xu J, Wang X, Zhang C, Yu Z, Liu J, Tai Z, Luo Z, Yi X, Zhong Z. Whole exome and transcriptome sequencing reveal clonal evolution and exhibit immune-related features in metastatic colorectal tumors. Cell Death Discov. 2021;7(1):222.PubMedPubMedCentralCrossRef
51.
Wang HW, Yan XL, Wang LJ, Zhang MH, Yang CH, Wei L, Jin KM, Bao Q, Li J, Wang K, et al. Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases. J Transl Med. 2021;19(1):313.PubMedPubMedCentralCrossRef
52.
Vasudevan A, Baruah PS, Smith JC, Wang Z, Sayles NM, Andrews P, Kendall J, Leu J, Chunduri NK, Levy D, et al. Single-Chromosomal gains can function as metastasis suppressors and promoters in colon cancer. Dev Cell. 2020;52(4):413–28.PubMedPubMedCentralCrossRef
53.
Li H, Wang J, Yi Z, Li C, Wang H, Zhang J, Wang T, Nan P, Lin F, Xu D, et al. CDK12 inhibition enhances sensitivity of HER2+ breast cancers to HER2-tyrosine kinase inhibitor via suppressing PI3K/AKT. Eur J Cancer. 2021;145:92–108.PubMedCrossRef
54.
Pancione M, Giordano G, Remo A, Febbraro A, Sabatino L, Manfrin E, Ceccarelli M, Colantuoni V. Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis. J Immunol Res. 2014;2014: 686879.PubMedPubMedCentralCrossRef
55.
Banerjee R, Smith J, Eccles MR, Weeks RJ, Chatterjee A. Epigenetic basis and targeting of cancer metastasis. Trends Cancer. 2022;8(3):226–41.PubMedCrossRef
56.
Hogg SJ, Beavis PA, Dawson MA, Johnstone RW. Targeting the epigenetic regulation of antitumour immunity. Nat Rev Drug Discov. 2020;19(11):776–800.PubMedCrossRef
57.
Jung G, Hernandez-Illan E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol. 2020;17(2):111–30.PubMedPubMedCentralCrossRef
58.
Wang L, Wang E, Prado Balcazar J, Wu Z, Xiang K, Wang Y, Huang Q, Negrete M, Chen KY, Li W, et al. Chromatin remodeling of colorectal cancer liver metastasis is mediated by an HGF-PU 1-DPP4 Axis. Adv Sci. 2021;8(19):e2004673.CrossRef
59.
Wang S, Gao S, Zeng Y, Zhu L, Mo Y, Wong CC, Bao Y, Su P, Zhai J, Wang L, et al. N6-Methyladenosine reader YTHDF1 Promotes ARHGEF2 translation and RhoA signaling in colorectal cancer. Gastroenterology. 2022;162(4):1183–96.PubMedCrossRef
60.
Chen RX, Chen X, Xia LP, Zhang JX, Pan ZZ, Ma XD, Han K, Chen JW, Judde JG, Deas O, et al. N(6)-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun. 2019;10(1):4695.PubMedPubMedCentralCrossRef
61.
Bleau AM, Redrado M, Nistal-Villan E, Villalba M, Exposito F, Redin E, de Aberasturi AL, Larzabal L, Freire J, Gomez-Roman J, et al. miR-146a targets c-met and abolishes colorectal cancer liver metastasis. Cancer Lett. 2018;414:257–67.PubMedCrossRef
62.
Zheng X, Chen L, Zhou Y, Wang Q, Zheng Z, Xu B, Wu C, Zhou Q, Hu W, Wu C, et al. A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling. Mol Cancer. 2019;18(1):47.PubMedPubMedCentralCrossRef
63.
Yue B, Liu C, Sun H, Liu M, Song C, Cui R, Qiu S, Zhong M. A positive feed-forward loop between LncRNA-CYTOR and Wnt/beta-catenin signaling promotes metastasis of colon cancer. Mol Ther. 2018;26(5):1287–98.PubMedPubMedCentralCrossRef
64.
65.
66.
Udali S, De Santis D, Ruzzenente A, Moruzzi S, Mazzi F, Beschin G, Tammen SA, Campagnaro T, Pattini P, Olivieri O, et al. DNA methylation and hydroxymethylation in primary colon cancer and synchronous hepatic metastasis. Front Genet. 2017;8:229.PubMedCrossRef
67.
Mahdi MR, Georges RB, Ali DM, Bedeer RF, Eltahry HM, Gabr AHZ, Berger MR. Modulation of the endothelin system in colorectal cancer liver metastasis: influence of epigenetic mechanisms? Front Pharmacol. 2020;11:180.PubMedPubMedCentralCrossRef
68.
Zhang KL, Zhu WW, Wang SH, Gao C, Pan JJ, Du ZG, Lu L, Jia HL, Dong QZ, Chen JH, et al. Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer. Theranostics. 2021;11(13):6560–72.PubMedPubMedCentralCrossRef
69.
Chen Y, Lin Y, Shu Y, He J, Gao W. Interaction between N(6)-methyladenosine (m(6)A) modification and noncoding RNAs in cancer. Mol Cancer. 2020;19(1):94.PubMedPubMedCentralCrossRef
70.
Lee J, Hong HK, Peng SB, Kim TW, Lee WY, Yun SH, Kim HC, Liu J, Ebert PJ, Aggarwal A, et al. Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors. Sci Rep. 2020;10(1):14919.PubMedPubMedCentralCrossRef
71.
Mouillet JF, Donker RB, Mishima T, Cronqvist T, Chu T, Sadovsky Y. The unique expression and function of miR-424 in human placental trophoblasts. Biol Reprod. 2013;89(2):25.PubMedPubMedCentralCrossRef
72.
Zhu ED, Li N, Li BS, Li W, Zhang WJ, Mao XH, Guo G, Zou QM, Xiao B. miR-30b, down-regulated in gastric cancer, promotes apoptosis and suppresses tumor growth by targeting plasminogen activator inhibitor-1. PLoS ONE. 2014;9(8): e106049.PubMedPubMedCentralCrossRef
73.
Chen T, You Y, Jiang H, Wang ZZ. Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol. 2017;232(12):3261–72.PubMedPubMedCentralCrossRef
74.
75.
Miyazaki T, Chung S, Sakai H, Ohata H, Obata Y, Shiokawa D, Mizoguchi Y, Kubo T, Ichikawa H, Taniguchi H, et al. Stemness and immune evasion conferred by the TDO2-AHR pathway are associated with liver metastasis of colon cancer. Cancer Sci. 2022;113(1):170–81.PubMedCrossRef
76.
Dieter SM, Ball CR, Hoffmann CM, Nowrouzi A, Herbst F, Zavidij O, Abel U, Arens A, Weichert W, Brand K, et al. Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell. 2011;9(4):357–65.PubMedCrossRef
77.
Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 2011;481(7379):85–9.PubMedCrossRef
78.
79.
80.
Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauss A, Blaudszun AR, Yevsa T, Fricke S, Kossatz-Boehlert U. Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front Immunol. 2020;11:1280.PubMedPubMedCentralCrossRef
81.
de SousaSousa e F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD, Hung J, Anderson JE, Storm EE, Modrusan Z, Koeppen H, et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer. Nature. 2017;543(7647):676–80.CrossRef
82.
Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, Apuzzo T, Sperduti I, Volpe S, Cocorullo G, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 2014;14(3):342–56.PubMedCrossRef
83.
Gao W, Chen L, Ma Z, Du Z, Zhao Z, Hu Z, Li Q. Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential. Gastroenterology. 2013;145(3):636–46.PubMedCrossRef
84.
Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, Sevillano M, Hernando-Momblona X, da Silva-Diz V, Munoz P, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8(5):511–24.PubMedCrossRef
85.
Qiu L, Yang X, Wu J, Huang C, Miao Y, Fu Z. HIST2H2BF potentiates the propagation of cancer stem cells via notch signaling to promote malignancy and liver metastasis in colorectal carcinoma. Front Oncol. 2021;11: 677646.PubMedPubMedCentralCrossRef
86.
Wang J, Xing Y, Wang Y, He Y, Wang L, Peng S, Yang L, Xie J, Li X, Qiu W, et al. A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer. J Exp Clin Cancer Res. 2019;38(1):422.PubMedPubMedCentralCrossRef
87.
88.
Milette S, Sicklick JK, Lowy AM, Brodt P. Molecular pathways: targeting the microenvironment of liver metastases. Clin Cancer Res. 2017;23(21):6390–9.PubMedPubMedCentralCrossRef
89.
Pretzsch E, Bosch F, Neumann J, Ganschow P, Bazhin A, Guba M, Werner J, Angele M. Mechanisms of metastasis in colorectal cancer and metastatic organotropism: hematogenous versus peritoneal spread. J Oncol. 2019;2019:7407190.PubMedPubMedCentralCrossRef
90.
Zhu X, Wang F, Wu X, Li Z, Wang Z, Ren X, Zhou Y, Song F, Liang Y, Zeng Z, et al. FBX8 promotes metastatic dormancy of colorectal cancer in liver. Cell Death Dis. 2020;11(8):622.PubMedPubMedCentralCrossRef
91.
Brodt P. Role of the microenvironment in liver metastasis: from pre- to prometastatic niches. Clin Cancer Res. 2016;22(24):5971–82.PubMedCrossRef
92.
Wen XQ, Qian XL, Sun HK, Zheng LL, Zhu WQ, Li TY, Hu JP. MicroRNAs: multifaceted regulators of colorectal cancer metastasis and clinical applications. Onco Targets Ther. 2020;13:10851–66.PubMedPubMedCentralCrossRef
93.
Vidal-Vanaclocha F, Crende O, de DurangoGarcia C, Herreros-Pomares A, Lopez-Domenech S, Gonzalez A, Ruiz-Casares E, Vilboux T, Caruso R, Duran H, et al. Liver prometastatic reaction: stimulating factors and responsive cancer phenotypes. Semin Cancer Biol. 2021;71:122–33.PubMedCrossRef
94.
Zhang Y, Zhao Y, Li Q, Wang Y. Macrophages, as a promising strategy to targeted treatment for colorectal cancer metastasis in tumor immune microenvironment. Front Immunol. 2021;12: 685978.PubMedPubMedCentralCrossRef
95.
96.
Paauwe M, Schoonderwoerd MJA, Helderman R, Harryvan TJ, Groenewoud A, van Pelt GW, Bor R, Hemmer DM, Versteeg HH, Snaar-Jagalska BE, et al. Endoglin expression on cancer-associated fibroblasts regulates invasion and stimulates colorectal cancer metastasis. Clin Cancer Res. 2018;24(24):6331–44.PubMedCrossRef
97.
98.
Hu JL, Wang W, Lan XL, Zeng ZC, Liang YS, Yan YR, Song FY, Wang FF, Zhu XH, Liao WJ, et al. CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol Cancer. 2019;18(1):91.PubMedPubMedCentralCrossRef
99.
Tan HX, Gong WZ, Zhou K, Xiao ZG, Hou FT, Huang T, Zhang L, Dong HY, Zhang WL, Liu Y, et al. CXCR4/TGF-beta1 mediated hepatic stellate cells differentiation into carcinoma-associated fibroblasts and promoted liver metastasis of colon cancer. Cancer Biol Ther. 2020;21(3):258–68.PubMedCrossRef
100.
Garner H, de Visser KE. Immune crosstalk in cancer progression and metastatic spread: a complex conversation. Nat Rev Immunol. 2020;20(8):483–97.PubMedCrossRef
101.
Jiang HY, Najmeh S, Martel G, MacFadden-Murphy E, Farias R, Savage P, Leone A, Roussel L, Cools-Lartigue J, Gowing S, et al. Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis. Protein Cell. 2020;11(3):187–201.PubMedPubMedCentralCrossRef
102.
Xing W, Xiao Y, Lu X, Zhu H, He X, Huang W, Lopez ES, Wong J, Ju H, Tian L, et al. GFI1 downregulation promotes inflammation-linked metastasis of colorectal cancer. Cell Death Differ. 2017;24(5):929–43.PubMedPubMedCentralCrossRef
103.
Li M, Lai X, Zhao Y, Zhang Y, Li M, Li D, Kong J, Zhang Y, Jing P, Li H, et al. Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by regulating tumor associate macrophages polarization. Cell Death Dis. 2018;9(2):248.PubMedPubMedCentralCrossRef
104.
Wang D, Wang X, Si M, Yang J, Sun S, Wu H, Cui S, Qu X, Yu X. Exosome-encapsulated miRNAs contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett. 2020;474:36–52.PubMedCrossRef
105.
Grossman JG, Nywening TM, Belt BA, Panni RZ, Krasnick BA, DeNardo DG, Hawkins WG, Goedegebuure SP, Linehan DC, Fields RC. Recruitment of CCR2(+) tumor associated macrophage to sites of liver metastasis confers a poor prognosis in human colorectal cancer. Oncoimmunology. 2018;7(9): e1470729.PubMedPubMedCentralCrossRef
106.
Liu Y, Zhang Q, Xing B, Luo N, Gao R, Yu K, Hu X, Bu Z, Peng J, Ren X, et al. Immune phenotypic linkage between colorectal cancer and liver metastasis. Cancer Cell. 2022;40(4):424-437.e425.PubMedCrossRef
107.
Wu Y, Yang S, Ma J, Chen Z, Song G, Rao D, Cheng Y, Huang S, Liu Y, Jiang S, et al. Spatiotemporal immune landscape of colorectal cancer liver metastasis at single-cell level. Cancer Discov. 2022;12(1):134–53.PubMedCrossRef
108.
Thomassen I, van Gestel YR, Lemmens VE, de Hingh IH. Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origin. Dis Colon Rectum. 2013;56(12):1373–80.PubMedCrossRef
109.
110.
Lang H, Baumgart J, Heinrich S, Tripke V, Passalaqua M, Maderer A, Galle PR, Roth W, Kloth M, Moehler M. Extended molecular profiling improves stratification and prediction of survival after resection of colorectal liver metastases. Ann Surg. 2019;270(5):799–805.PubMedCrossRef
111.
Tóth C, Sükösd F, Valicsek E, Herpel E, Schirmacher P, Renner M, Mader C, Tiszlavicz L, Kriegsmann J. Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer. Int J Mol Med. 2017;40(5):1457–65.PubMedPubMedCentralCrossRef
112.
Olsen LM, Fiehn AK, Hasselby JP. ERCC1 expression in advanced colorectal cancer and matched liver metastases. Pathol Res Pract. 2020;216(3): 152826.PubMedCrossRef
113.
Aykut B, Ochs M, Radhakrishnan P, Brill A, Hocker H, Schwarz S, Weissinger D, Kehm R, Kulu Y, Ulrich A, et al. EMX2 gene expression predicts liver metastasis and survival in colorectal cancer. BMC Cancer. 2017;17(1):555.PubMedPubMedCentralCrossRef
114.
Aust N, Schule S, Altendorf-Hofmann AK, Chen Y, Knosel T, Dirsch O, Settmacher U, Weise A, Mrasek K, Liehr T. Loss of chromosome 4 correlates with better long-term survival and lower relapse rate after R0-resection of colorectal liver metastases. J Cancer Res Clin Oncol. 2013;139(11):1861–7.PubMedCrossRef
115.
Rehman AH, Jones RP, Poston G. Prognostic and predictive markers in liver limited stage IV colorectal cancer. Eur J Surg Oncol. 2019;45(12):2251–6.PubMedCrossRef
116.
Sun L, Liu X, Pan B, Hu X, Zhu Y, Su Y, Guo Z, Zhang G, Xu M, Xu X, et al. Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis. J Cancer. 2020;11(3):630–7.PubMedPubMedCentralCrossRef
117.
Xu H, Wang C, Song H, Xu Y, Ji G. RNA-Seq profiling of circular RNAs in human colorectal cancer liver metastasis and the potential biomarkers. Mol Cancer. 2019;18(1):8.PubMedPubMedCentralCrossRef
118.
Zhi Q, Wan D, Ren R, Xu Z, Guo X, Han Y, Liu F, Xu Y, Qin L, Wang Y. Circular RNA profiling identifies circ102049 as a key regulator of colorectal liver metastasis. Mol Oncol. 2021;15(2):623–41.PubMedCrossRef
119.
120.
Kong H, Wu Y, Zhu M, Zhai C, Qian J, Gao X, Wang S, Hou Y, Lu S, Zhu H. Long non-coding RNAs: novel prognostic biomarkers for liver metastases in patients with early stage colorectal cancer. Oncotarget. 2016;7(31):50428–36.PubMedPubMedCentralCrossRef
121.
Yang X, Zhang S, He C, Xue P, Zhang L, He Z, Zang L, Feng B, Sun J, Zheng M. METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Mol Cancer. 2020;19(1):46.PubMedPubMedCentralCrossRef
122.
Gao W, Chen Y, Yang J, Zhuo C, Huang S, Zhang H, Shi Y. Clinical perspectives on liquid biopsy in metastatic colorectal cancer. Front Genet. 2021;12: 634642.PubMedPubMedCentralCrossRef
123.
Allen JE, Saroya BS, Kunkel M, Dicker DT, Das A, Peters KL, Joudeh J, Zhu J, El-Deiry WS. Apoptotic circulating tumor cells (CTCs) in the peripheral blood of metastatic colorectal cancer patients are associated with liver metastasis but not CTCs. Oncotarget. 2014;5(7):1753–60.PubMedCrossRef
124.
Song Z, Chen E, Qian J, Xu J, Cao G, Zhou W, Wang F, Chen M, Xu D, Wang X, et al. Serum chitinase activity prognosticates metastasis of colorectal cancer. BMC Cancer. 2019;19(1):629.PubMedPubMedCentralCrossRef
125.
Garcia-Alfonso P, Ferrer A, Gil S, Duenas R, Perez MT, Molina R, Capdevila J, Safont MJ, Castanon C, Cano JM, et al. Neoadjuvant and conversion treatment of patients with colorectal liver metastasis: the potential role of bevacizumab and other antiangiogenic agents. Target Oncol. 2015;10(4):453–65.PubMedPubMedCentralCrossRef
126.
127.
Alhumaid A, AlYousef Z, Bakhsh HA, AlGhamdi S, Aziz MA. Emerging paradigms in the treatment of liver metastases in colorectal cancer. Crit Rev Oncol Hematol. 2018;132:39–50.PubMedCrossRef
128.
Saad AM, Abdel-Rahman O. Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases. Expert Opin Pharmacother. 2019;20(14):1767–75.PubMedCrossRef
129.
Punt CJ, Koopman M, Vermeulen L. From tumour heterogeneity to advances in precision treatment of colorectal cancer. Nat Rev Clin Oncol. 2017;14(4):235–46.PubMedCrossRef
130.
Sottoriva A, Kang H, Ma Z, Graham TA, Salomon MP, Zhao J, Marjoram P, Siegmund K, Press MF, Shibata D, et al. A Big Bang model of human colorectal tumor growth. Nat Genet. 2015;47(3):209–16.PubMedPubMedCentralCrossRef
131.
Singovski G, Bernal C, Kuciak M, Siegl-Cachedenier I, Conod A. Ruiz i Altaba A: in vivo epigenetic reprogramming of primary human colon cancer cells enhances metastases. J Mol Cell Biol. 2016;8(2):157–73.PubMedCrossRef
132.
Hu M, Zhou X, Wang Y, Guan K, Huang L. Relaxin-FOLFOX-IL-12 triple combination therapy engages memory response and achieves long-term survival in colorectal cancer liver metastasis. J Control Release. 2020;319:213–21.PubMedCrossRef
133.
Poureau P-G, Metges J-P. Fundamentals of digestive cancers immunology, especially gastric and hepatocellular carcinomasfondamentaux de l’immunologie des cancers digestifs (Gastriques et Hépatocellulaires). Oncologie. 2021;23(1):47–59.CrossRef
134.
Xing C, Li H, Li RJ, Yin L, Zhang HF, Huang ZN, Cheng Z, Li J, Wang ZH, Peng HL. The roles of exosomal immune checkpoint proteins in tumors. Mil Med Res. 2021;8(1):56.PubMedPubMedCentral
135.
Zhang Y, Song J, Zhao Z, Yang M, Chen M, Liu C, Ji J, Zhu D. Single-cell transcriptome analysis reveals tumor immune microenvironment heterogenicity and granulocytes enrichment in colorectal cancer liver metastases. Cancer Lett. 2020;470:84–94.PubMedCrossRef
136.
137.
Chen DL, Lu YX, Zhang JX, Wei XL, Wang F, Zeng ZL, Pan ZZ, Yuan YF, Wang FH, Pelicano H, et al. Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression. Theranostics. 2017;7(19):4836–49.PubMedPubMedCentralCrossRef
Metadata
Title
Intracellular and extracellular factors of colorectal cancer liver metastasis: a pivotal perplex to be fully elucidated
Authors
Yaru Niu
Wenwei Yang
Haili Qian
Yongkun Sun
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02766-w

Other articles of this Issue 1/2022

Cancer Cell International 1/2022 Go to the issue

Primary research

E2F6/KDM5C promotes SF3A3 expression and bladder cancer progression through a specific hypomethylated DNA promoter

Review

MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy

Primary research

Exosomes derived from M2 type tumor-associated macrophages promote osimertinib resistance in non-small cell lung cancer through MSTRG.292666.16-miR-6836-5p-MAPK8IP3 axis

Primary research

miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy

Research

Increased expression of miR-194-5p through the circPVRL3/miR-194-5p/SOCS2 axis promotes proliferation and metastasis in pancreatic ductal adenocarcinoma by activating the PI3K/AKT signaling pathway

Primary research

MiR-323a-3p acts as a tumor suppressor by suppressing FMR1 and predicts better esophageal squamous cell carcinoma outcome
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits