Expanding Roles of ZEB Factors in Tumorigenesis and Tumor Progression

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2011 Oct 22

PMID 22016835

Citations 97

Authors

Ester Sanchez-Tillo

Laura Siles

Oriol de Barrios

Miriam Cuatrecasas

Eva C Vaquero

Antoni Castells

Antonio Postigo

Affiliations

Soon will be listed here.

Abstract

The ZEB family of transcription factors regulates key factors during embryonic development and cell differentiation but their role in cancer biology has only more recently begun to be recognized. Early evidence showed that ZEB proteins induce an epithelial-to-mesenchymal transition linking their expression with increased aggressiveness and metastasis in mice models and a wide range of primary human carcinomas. Reports over the last few years have found that ZEB proteins also play critical roles in the maintenance of cancer cell stemness, control of replicative senescence, tumor angiogenesis, overcoming of oncogenic addiction and resistance to chemotherapy. These expanding roles in tumorigenesis and tumor progression set ZEB proteins as potential diagnostic, prognostic and therapeutic targets.

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References

Nishimura G, Manabe I, Tsushima K, Fujiu K, Oishi Y, Imai Y . DeltaEF1 mediates TGF-beta signaling in vascular smooth muscle cell differentiation. Dev Cell. 2006; 11(1):93-104. DOI: 10.1016/j.devcel.2006.05.011. View

Bindels S, Mestdagt M, Vandewalle C, Jacobs N, Volders L, Noel A . Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene. 2006; 25(36):4975-85. DOI: 10.1038/sj.onc.1209511. View

Aigner K, Descovich L, Mikula M, Sultan A, Dampier B, Bonne S . The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression. FEBS Lett. 2007; 581(8):1617-24. PMC: 2938730. DOI: 10.1016/j.febslet.2007.03.026. View

Franklin A, Jetton T, Shelton K, Magnuson M . BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription. Mol Cell Biol. 1994; 14(10):6773-88. PMC: 359208. DOI: 10.1128/mcb.14.10.6773-6788.1994. View

Chinnadurai G . The transcriptional corepressor CtBP: a foe of multiple tumor suppressors. Cancer Res. 2009; 69(3):731-4. PMC: 4367538. DOI: 10.1158/0008-5472.CAN-08-3349. View

Graham T, Zhau H, Odero-Marah V, Osunkoya A, Kimbro K, Tighiouart M . Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 2008; 68(7):2479-88. DOI: 10.1158/0008-5472.CAN-07-2559. View

Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N . A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009; 15(6):489-500. PMC: 2743093. DOI: 10.1016/j.ccr.2009.03.022. View

Shi Y, Sawada J, Sui G, Affar E, Whetstine J, Lan F . Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature. 2003; 422(6933):735-8. DOI: 10.1038/nature01550. View

Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M . DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene. 2005; 24(14):2375-85. DOI: 10.1038/sj.onc.1208429. View

10.

Williams T, Moolten D, Burlein J, Romano J, Bhaerman R, Godillot A . Identification of a zinc finger protein that inhibits IL-2 gene expression. Science. 1991; 254(5039):1791-4. DOI: 10.1126/science.1840704. View

11.

Yilmaz M, Christofori G . EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009; 28(1-2):15-33. DOI: 10.1007/s10555-008-9169-0. View

12.

Sekido R, Murai K, Kamachi Y, Kondoh H . Two mechanisms in the action of repressor deltaEF1: binding site competition with an activator and active repression. Genes Cells. 1998; 2(12):771-83. DOI: 10.1046/j.1365-2443.1997.1570355.x. View

13.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

14.

Ponticos M, Partridge T, Black C, Abraham D, Bou-Gharios G . Regulation of collagen type I in vascular smooth muscle cells by competition between Nkx2.5 and deltaEF1/ZEB1. Mol Cell Biol. 2004; 24(14):6151-61. PMC: 434261. DOI: 10.1128/MCB.24.14.6151-6161.2004. View

15.

Krishnamachary B, Zagzag D, Nagasawa H, Rainey K, Okuyama H, Baek J . Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res. 2006; 66(5):2725-31. DOI: 10.1158/0008-5472.CAN-05-3719. View

16.

Liu Y, Costantino M, Montoya-Durango D, Higashi Y, Darling D, Dean D . The zinc finger transcription factor ZFHX1A is linked to cell proliferation by Rb-E2F1. Biochem J. 2007; 408(1):79-85. PMC: 2049079. DOI: 10.1042/BJ20070344. View

17.

Higashikawa K, Yoneda S, Tobiume K, Taki M, Shigeishi H, Kamata N . Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma. Cancer Res. 2007; 67(19):9207-13. DOI: 10.1158/0008-5472.CAN-07-0932. View

18.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

19.

Witta S, Gemmill R, Hirsch F, Coldren C, Hedman K, Ravdel L . Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res. 2006; 66(2):944-50. DOI: 10.1158/0008-5472.CAN-05-1988. View

20.

Wang J, Scully K, Zhu X, Cai L, Zhang J, Prefontaine G . Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature. 2007; 446(7138):882-7. DOI: 10.1038/nature05671. View