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European Surgery
Published in: European Surgery 5/2017

Open Access 01-10-2017 | review

Notch and its oncogenic activity in human malignancies

Authors: Marlena Brzozowa-Zasada, Adam Piecuch, Marek Michalski, Oliwia Segiet, Józef Kurek, Marzena Harabin-Słowińska, Romuald Wojnicz

Published in: European Surgery | Issue 5/2017

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Summary

Background

Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown.

Methods

This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis.

Results

Numerous reports have indicated that alterations in Notch signaling and its oncogenic activity were originally associated with the pathogenesis of T‑cell acute lymphoblastic leukemia/lymphoma (T-ALL), an aggressive hematologic tumor affecting children and adolescents. The possibility that Notch could play a significant role in human breast cancer development comes from studies on mouse mammary tumor virus-induced cancer. Numerous findings over the past several years have indicated that alterations in Notch signaling are also responsible for ovarian cancer development. Mention should also be made of the connection between expression of Notch 3 and increased resistance to chemotherapy, which remains a major obstacle to successful treatment. Notch as an oncogenic factor is also involved in the development of colon cancer, lung carcinoma and Kaposi’s sarcoma.

Conclusion

Notch is a binary cell fate determinant and its overexpression has been described as oncogenic in a wide array of human malignancies. This finding led to interest in therapeutically targeting this pathway, especially by the use of gamma-secretase inhibitors (GSIs) blocking the cleavage of Notch receptors at the cell membrane by the inhibition of Notch intracellular domain (NICD) releasing. Preclinical cancer models have revealed that GSIs suppress the growth of cancers such as pancreatic, breast and lung cancer.
Literature
1.
Bray S. Notch signaling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006;7:678–89.CrossRefPubMed
2.
Purrow B. Notch signaling in embryology and cancer. Adv Exp Med Biol. 2012;727:174–315.CrossRef
3.
Allenspach EJ, Maillard I, Aster JC, Pear WS. Notch signaling in cancer. Cancer Biol Ther. 2002;1:466–76.CrossRefPubMed
4.
Brzozowa M, Wojnicz R, Kowalczyk-Ziomek G, Helewski K, et al. The Notch ligand Delta-like 4 (DLL4) as a target in angiogenesis-based cancer therapy? Contemp Oncol (Pozn). 2013;17(3):234–7.
5.
Brzozowa M, Mielańczyk L, Michalski M, Malinowski L, Kowalczyk-Ziomek G, Helewski K, et al. Role of Notch signaling pathway in gastric cancer pathogenesis. Contemp Oncol (Pozn). 2013;17:1–5.
6.
Brzozowa-Zasada M, Piecuch A, Dittfeld A, Mielańczyk L, Michalski M, Wyrobiec G, et al. Notch signaling pathway as an oncogenic factor involved in cancer development. Contemp Oncol (Pozn). 2016;20:267–72.
7.
Radtke F, Raj K. The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer. 2003;3:756–67.CrossRefPubMed
8.
Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002;1:75–87.CrossRefPubMed
9.
Ellisen L, Bird J, West D, Soreng A, Reynolds T, Smith S, et al. TAN-1, the human homolog of the drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66:649–61.CrossRefPubMed
10.
Weng A, Ferrando A, Lee W, Morris J, Silverman I, Sanchez-Irizarry C, et al. Activating mutations of Notch1 in human T cell acute lymphoblstic leukemia. Science. 2004;306:269–71.CrossRefPubMed
11.
Haydu J, De Keersmaecker K, Duff M, Paietta E, Racevskis J, Wiernik P, et al. An activating intragenic deletion in Notch1 in human T‑ALL. Blood. 2012;119:5211–4.CrossRefPubMedPubMedCentral
12.
Sulis M, Williams O, Palomer T, Tosello V, Pallikuppam S, Real P, et al. Notch1 extracellular juxtamembrane expansion mutations in T‑ALL. Blood. 2008;112:733–40.CrossRefPubMedPubMedCentral
13.
Thompson B, Buonamici S, Sulis M, Palomer T, Viliams T, Basso G, et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med. 2007;204:1825–35.CrossRefPubMedPubMedCentral
14.
O’Neil J, Grim J, Strack P, Rao S, Tibbits D, Winter C, et al. FBW7 mutations in leukemic cells mediate Notch pathway activation and resistance to gamma-secretase inhibitors. J Exp Med. 2007;204:1813–24.CrossRefPubMedPubMedCentral
15.
Malyukowa A, Dohda T, von der Lehr N, Akhoodi S, Corcoran M, Heyman M, et al. The tumor suppressor gene hCDC4 is frequently mutated in human T‑cell acute lymphoblastic leukemia with functional consequence for Notch signaling. Cancer Res. 2007;67:5611–6.CrossRef
16.
Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser RS, et al. SCF (FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature. 2011;471:104–9.CrossRefPubMedPubMedCentral
17.
Tan Y, Sangfelt O, Spruck C. The Fbxw7/hCdc4 tumor suppressor in human cancer. Cancer Lett. 2008;271:1–12.CrossRefPubMed
18.
Sharma VM, Draheim KM, Kelliher MA. The Notch1/c-myc pathway in T cell leukemia. Cell Cycle. 2007;6(8):927–30.CrossRefPubMed
19.
Chan SM, Weng AP, Tibshirani R, Aster JC, Utz PJ. Notch signals positively regulate activity of the mTOR pathway in T‑cell acute lymphoblstic leukemia. Blood. 2007;110:278–86.CrossRefPubMedPubMedCentral
20.
Ciofani M, Zúniga-Pflucker JC. Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol. 2005;6:881–8.CrossRefPubMed
21.
Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T‑cell leukemia. Nat Med. 2007;13:1203–10.CrossRefPubMedPubMedCentral
22.
Gonzales-Garcia S, Garcia-Peydro M, Martin-Gayo E, Ballestar E, Esteller M, Bornstein R. CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopeiesis and leukemia. J Exp Med. 2009;206:779–91.CrossRef
23.
Medyouf H, Gusscott S, Wang H, Tseng JC, Wai C, Nemirovsky O, et al. High-level IGF1R expression is required for leukemia-initiating cell activity in T‑ALL and is supported by notch signaling. J Exp Med. 2011;208:1809–22.CrossRefPubMedPubMedCentral
24.
25.
Dohda T, Maljukova A, Liu L, Heyman M, Grander D, Brodin D, et al. Notch signaling induces SKP2 expression and promotes reduction of p27Kip1 in T‑cell acute lymphoblastic leukemia cell lines. Exp Cell Res. 2007;313:3141–52.CrossRefPubMed
26.
Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, Marqolin A, et al. NOTCH1 directly regulates c‑MYC and activates a feed-forward-loop transcriptional network promoting leukemic growth. Proc Natl Acad Sci USA. 2006;103:18261–6.CrossRefPubMedPubMedCentral
27.
28.
Ntziachristos P, Tsiriqos A, Van Vlierberghe P, Nedjic J, Trimarchi T, Flaherty MS, et al. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat Med. 2012;18:298–301.CrossRefPubMedPubMedCentral
29.
Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig T, Tolle G, et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T‑cell lymphoblastic leukemia. Blood. 2006;108:1151–7.CrossRefPubMed
30.
Park MJ, Taki T, Oda M, Watanabe T, Yumura-Yagi K, Kobayashi R, et al. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgin lymphoma. Br J Haematol. 2009;145:198–206.CrossRefPubMed
31.
Mansour MR, Sulis ML, Duke V, Foroni L, Jenkins S, Koo K, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T‑cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol. 2009;27:4352–6.CrossRefPubMedPubMedCentral
32.
Abdelali BR, Asnafi V, Lequay T, Boissel N, Buzyn A, Chevallier P, et al. Pediatric-inspired intensified therapy of adult T‑ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study. Blood. 2011;118:5099–107.CrossRefPubMed
33.
Mori M, Tottone L, Quaglio D, Zhdanovskaya N, Ingallina C, Fusto M. Identification of a novel chalcone derivative that inhibits Notch signaling in T‑cell acute lymphoblastic leukemia. Sci Rep. 2017;7:2213.CrossRefPubMedPubMedCentral
34.
35.
Mikaelian I, Blades N, Churchill GA, Fancher K, Knowless BB, Eppig JT, et al. Proteotypic classification of spontaneous transgenic mammary neoplasms. Breast Cancer Res. 2004;6:668–79.CrossRef
36.
Scully OJ, Bay B‑H, Yip G, Yu Y. Breast cancer metastasis. Cancer Genomics Proteomics. 2012;9:311–20.PubMed
37.
Zardawi SJ, Zardawi I, McNeil CM, Millar EKA, McLeod D, Morey AL, et al. High Notch1 protein expression is an early event in breast cancer development and is associated with the HER2 molecular subtype. Histopathology. 2010;56:286–96.CrossRefPubMed
38.
Lee SH, Jeong EG, Yoo NJ, Lee SH. Mutational analysis of NOTCH1, 2, 3, and 4 genes in common solid cancers and acute leukemias. APMIS. 2007;115:1357–63.CrossRefPubMed
39.
Rizzo P, Miao H, D’Souza G, Osipo C, Yun J, Zhao H, et al. Cross-talk between notch and estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res. 2008;68:5226–35.CrossRefPubMedPubMedCentral
40.
Mittal S, Subramanyam D, Dey D, Kumar RV, Rangarajan A. Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis. Mol Cancer. 2009;8:128.CrossRefPubMedPubMedCentral
41.
Bolos V, Mira E, Martinez-Poveda B, Luxan G, Caňamero M, Martinez-AC, et al. Notch activation stimulates migration of breast cancer suggests novel therapeutic approaches. Cancer Res. 2008;68:5226–35.CrossRef
42.
Shao S, Zhao X, Zhang X, Luo M, Zuo X, Huang S, et al. Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner. Mol Cancer. 2015;14:28.CrossRefPubMedPubMedCentral
43.
44.
Bednarz-Knoll N, Efstathiou A, Gotzhein F, Wikman H, Mueller V, Kang Y, et al. Potential involvement of Jagged1 in metastatic progression of human breast carcinomas. Clin Chem. 2016;62:378–86.CrossRefPubMed
45.
Dickson BC, Mulligan AM, Zhang H, Lockwood G, O’Malley FP, Egan SE, et al. High-level JAG1 mRNA and protein predict poor outcome in breast cancer. Mod Pathol. 2007;20:685–93.CrossRefPubMed
46.
Sethi N, Dai X, Winter CG, Kang Y. Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell. 2011;19:192–205.CrossRefPubMedPubMedCentral
47.
Santagata S, Demichelis F, Riva A, Varambally S, Hofer MD, Kutok JL, et al. JAGGED1 expression is associated with prostate cancer metastatsis and recourence. Cancer Res. 2004;64:6854–7.CrossRefPubMed
48.
Zhang XHF, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell. 2009;16:67–78.CrossRefPubMedPubMedCentral
49.
50.
51.
Jung SG, Kwon YD, Song JA, Back MJ, Lee SY, Lee C, et al. Prognostic significance of Notch3 gene expression in ovarian serous carcinoma. Cancer Sci. 2010;101:1977–83.CrossRefPubMed
52.
Park JT, Chen X, Troppe CG, Davidson B, le Shih M, Wang TL. Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am J Path. 2010;177:1087–94.CrossRefPubMedPubMedCentral
53.
Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, et al. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol. 2012;138:535–44.CrossRefPubMed
54.
Gupta N, Xu Z, El-Sehemy A, Steed H, Fu Y. Notch3 induces epithelial-mesenchymal transition and attenuates carboplatin -induced apoptosis in ovarian cancer. Gynecol Oncol. 2013;130:200–6.CrossRefPubMed
55.
Kang H, Jeong JY, Song JY, Kim TH, Kim G, Huh JH. Notch-3 specific inhibition using siRNA knockdown or GSI sensitizes paclitaxel-resistant ovarian cancer cells. Mol Carcinog. 2016;55:1196–209.CrossRefPubMed
56.
57.
Rose SL, Kunnimalaiyaan M, Drenzek J, Seiler N. Notch1 signaling is active in ovarian cancer. Gynecol Oncol. 2010;117:130–3.CrossRefPubMed
58.
Fojo T. Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Updat. 2007;10:59–67.CrossRefPubMed
59.
Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer. 2010;127:1785–94.CrossRefPubMed
60.
Hwang JH, Voortman J, Giovanetti E, Steinberg SM, Leon LG, Kim YT, et al. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLOS ONE. 2010;5:e10630.CrossRefPubMedPubMedCentral
61.
Liu MX, Siu MKY, Liu SS, Yam JWP, Ngan HYS, Chan DW. Epigenetic silencing of microRNA-199b-5p is associated with acquired chemoresistance via activation of JAG1-Notch1 signaling in ovarian cancer. Oncotarget. 2014;5:944–58.CrossRefPubMed
62.
Zhou Y, Chen Q, Qin R, Zhang K, Li H. MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. Tumour Biol. 2014;35:12369–78.CrossRefPubMed
63.
Liang T, Guo Q, Li L, Cheng Y, Ren C, Zhang G. MicroRNA-433 inhibits migration and invasion of ovarian cancer cells via targeting Notch1. Neoplasma. 2016;63:696–704.CrossRefPubMed
64.
Chen Ch, Wang X, Huang S, Wang L, Han L, Yu S. Prognostic roles of Notch receptor mRNA expression in human ovarian cancer. Oncotarget. 2017;8:32731–40.PubMedPubMedCentral
65.
Zhang Y, Li B, Ji Z‑Z, Zheng P‑S. Notch 1 regulates the growth of human colon cancers. Cancer. 2010;116:5207–18.CrossRefPubMed
66.
Chu D, Li Y, Wang W, Zhao Q, Li J, Lu Y, et al. High level of Notch1 protein is associated with poor overall survival in colorectal cancer. Ann Surg Oncol. 2010;17:1337–42.CrossRefPubMed
67.
Brzozowa-Zasada M, Piecuch A, Segiet O, Stęplewska K, Gabriel A, Wojnicz R. The complex interplay between Notch signaling and Snail1 transcription factor in the regulation of epithelial-mesenchymal transition. Eur Surg. 2015;47:218–25.CrossRef
68.
Fender AW, Nutter JM, Fitzgerald TL, Bertrand FE, Sigounas G. Notch-1 promotes stemness and Epithelila to mesenchymal transition in colorectal cancer. J Cell Biochem. 2015;116:2517–27.CrossRefPubMed
69.
70.
Kim HA, Koo BK, Cho JH, Kim YY, Seong J, Chang HJ, et al. Notch1 counteracts WNT/β-catenin signaling through chromatin modification in colorectal cancer. J Clin Invest. 2012;122:3248–59.CrossRefPubMedPubMedCentral
71.
Chu D, Zhang Z, Zhou Y, Wang W, Li Y, Zhang H, et al. Notch1 and Notch2 have opposite prognostic effects on patients with colorectal cancer. Ann Oncol. 2011;22:2440–7.CrossRefPubMed
72.
Wang WJ, Yao Y, Jiang LL, Hu TH, Jq Ruan MZP, et al. Increased LEF1 expression and decreased notch2 expression are strong predictors of poor outcomes in colorectal cancer patients. Dis Markers. 2013;35:395–405.CrossRefPubMedPubMedCentral
73.
74.
75.
Indraccolo S, Minuzzo S, Masiero M, Pusceddu I, Persano L, Moserle L, et al. Cross-talk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy. Cancer Res. 2009;69:1314–23.CrossRefPubMed
76.
Paso A, Serafin V, Pilotto G, Lago C, Bellio C, Trusolino L, et al. Notch3 signaling regulates MUSASHI-1 expression in metastatic colorectal cancer cells. Cancer Res. 2014;74:2106–18.CrossRef
77.
Song G, Zhang Y, Wang L. MicroRNA-206 targets notch3, activates apoptosis, and inhibits tumor cell migration and focus formation. J Biol Chem. 2009;284:31921–7.CrossRefPubMedPubMedCentral
78.
Wang XW, Xi XQ, Wu J, Wan YY, Hui HX, Cao XF. MicroRNA-206 attenuates tumor proliferation and migration involving the downregulation of Notch3 in colorectal cancer. Oncol Rep. 2015;33:1402–10.CrossRefPubMed
79.
Westhoff B, Colaluca IN, D’Ario G, Donzelli M, Tosoni D, Volorio S, et al. Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA. 2009;106:22293–8.CrossRefPubMedPubMedCentral
80.
Donnem T, Andersen S, Al-shibili K, Al-Saad S, Busund L‑T, Bremnes RM. Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancer: coexpression of Notch-1 and vascular endothelial growth factor-A predicts poor survival. Cancer. 2010;116:5674–85.
81.
Allen TD, Rodriguez EM, Jones KD, Bishop JM. Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma. Cancer Res. 2011;71:6010–8.CrossRefPubMedPubMedCentral
82.
Hassan WA, Yoshida R, Kudoh S, Motooka Y, Ito T. Evaluation of role of Notch3 signaling pathway in human lung cancer cells. J Cancer Res Clin Oncol. 2016;142:981–93.CrossRefPubMed
83.
Haruki N, Kawaguchi KS, Eichenberger S, Massion PP, Olson S, Gonzales A, et al. Dominant-negative Notch3 receptor inhibits mitogen-activated protein kinase pathway and the growth of human lung cancers. Cancer Res. 2005;65:3555–61.CrossRefPubMed
84.
Konishi J, Kawaguchi KS, Vo H, Haruki N, Gonzales A, Carbone DP, et al. γ‑secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res. 2007;67:8051–7.CrossRefPubMed
85.
Konishi J, Yi F, Chen X, Vo H, Carbone DP, Dang TP. Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim. Oncogene. 2010;29:589–96.CrossRefPubMed
86.
Yuan X, Wu H, Xu H, Han N, Chu Q, Yu S, et al. Meta-analysis reveals the correlation of Notch signaling with non-small cell lung cancer progression and prognosis. Sci Rep. 2015;5:10338.CrossRefPubMedPubMedCentral
87.
88.
Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Cancer Res Clin Oncol. 2016;142:981–93.CrossRef
89.
Lu F, Zhou J, Wiedmer A, Madden K, Yuan Y, Lieberman PM. Chromatin remodeling of the Kaposi’s sarcoma-associated herpesvirus ORF50 promoter correlates with reactivation from latency. J Virol. 2003;77:11425–35.CrossRefPubMedPubMedCentral
90.
Lan K, Choudhuri T, Murakami M, Kuppers D, Robertson S. Intracellular activated Notch1 is critical for proliferation of Kaposi’s sarcoma-associated herpesvirus-associated B‑lymphoma cell lines in vitro. J Virol. 2006;80:6411–9.CrossRefPubMedPubMedCentral
91.
Curry CL, Reed LL, Golde TE, Miele L, Nickoloff BJ, Foreman KE. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi’s sarcoma tumor cells. Oncogene. 2005;24:6333–44.PubMed
92.
93.
Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet. 2003;33:416–21.CrossRefPubMed
94.
Gat U, DasGupta R, Degenstein L, Fuchs E. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell. 1998;95:605–14.CrossRefPubMed
95.
Zhu AJ, Watt FM. Beta catenin signaling modulates proliferative potential of human epidermal keratinocytes independently of interecellular adhesion. Development. 1999;126:2285–98.PubMed
96.
Devgan V, Mammucari C, Millar SE, Brisken C, Dotto GP. P21WAF1/CIP1 is a negative transcriptional regulator of Wnt4 expression downstream of Notch1 activation. Genes Dev. 2005;19:14851495.CrossRef
Metadata
Title
Notch and its oncogenic activity in human malignancies
Authors
Marlena Brzozowa-Zasada
Adam Piecuch
Marek Michalski
Oliwia Segiet
Józef Kurek
Marzena Harabin-Słowińska
Romuald Wojnicz
Publication date
01-10-2017
Publisher
Springer Vienna
Published in
European Surgery / Issue 5/2017
Print ISSN: 1682-8631
Electronic ISSN: 1682-4016
DOI
https://doi.org/10.1007/s10353-017-0491-z

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