Twist is a Transcriptional Repressor of E-cadherin Gene Expression in Breast Cancer

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2007 Dec 8

PMID 18062917

Citations 181

Authors

Farhad Vesuna

Paul van Diest

Ji Hshiung Chen

Venu Raman

Affiliations

Soon will be listed here.

Abstract

Twist is a basic helix loop helix protein that plays a role both in human development and in cancer biogenesis. While characterizing the effects of Twist on breast epithelial cell transformation, we identified E-cadherin as a target gene that is down-regulated by Twist. In this study, we demonstrate that Twist can transcriptionally repress E-cadherin in breast cancer cells. Using transient promoter assays, we show that Twist can down-regulate E-cadherin promoter activity by up to two folds. This is further supported by immunoblot analyses which indicates that over-expression of Twist decreases E-cadherin protein levels in breast cancer cell lines. Subsequently, chromatin immunoprecipitation performed on MCF-7/Twist and Hs578 T (high level of endogenous Twist expression) confirmed Twist binding to the E-cadherin promoter. Finally, the functional relevance of this regulation was verified by quantitative real-time PCR and immunohistochemistry on a cohort of breast cancer samples.

Citing Articles

Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.

Archer M, Lin K, Kolanukuduru K, Zhang J, Ben-David R, Kotula L Am J Clin Exp Urol. 2025; 12(6):331-351.

PMID: 39839748 PMC: 11744350. DOI: 10.62347/YFRP8901.

Bestrophin-4 relays HES4 and interacts with TWIST1 to suppress epithelial-to-mesenchymal transition in colorectal cancer cells.

Wang Z, Xia B, Qi S, Zhang X, Zhang X, Li Y Elife. 2024; 12.

PMID: 39699952 PMC: 11658771. DOI: 10.7554/eLife.88879.

ERβ-regulated circATP2B1/miR-204-3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma.

Wang H, Gao Y, Guo F, Zhou P, Ma Z, Chi K Transl Oncol. 2024; 51:102213.

PMID: 39586165 PMC: 11626627. DOI: 10.1016/j.tranon.2024.102213.

A Novel Class I HDAC Inhibitor, AW01178, Inhibits Epithelial-Mesenchymal Transition and Metastasis of Breast Cancer.

Liu X, Chen Y, Li Y, Shen Y, Dong S, Tan J Int J Mol Sci. 2024; 25(13).

PMID: 39000339 PMC: 11241290. DOI: 10.3390/ijms25137234.

LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder Cancer Cells through the Snail/E-cadherin Axis.

Wang L, Wang P, Liu B, Zhang H, Wei C, Xiong M Curr Med Sci. 2024; 44(4):726-734.

PMID: 38990449 DOI: 10.1007/s11596-024-2895-x.

References

Hirohashi S . Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998; 153(2):333-9. PMC: 1852964. DOI: 10.1016/S0002-9440(10)65575-7. View

Kwok W, Ling M, Lee T, Lau T, Zhou C, Zhang X . Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res. 2005; 65(12):5153-62. DOI: 10.1158/0008-5472.CAN-04-3785. View

El Ghouzzi V, Le Merrer M, Perrin-Schmitt F, Lajeunie E, Benit P, Renier D . Mutations of the TWIST gene in the Saethre-Chotzen syndrome. Nat Genet. 1997; 15(1):42-6. DOI: 10.1038/ng0197-42. View

Chen Z, Behringer R . twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev. 1995; 9(6):686-99. DOI: 10.1101/gad.9.6.686. View

Liu Y, Lee W, Wang C, Chao T, Chen Y, Chen J . Regulatory mechanisms controlling human E-cadherin gene expression. Oncogene. 2005; 24(56):8277-90. DOI: 10.1038/sj.onc.1208991. View

Vesuna F, Winnard Jr P, Raman V . Enhanced green fluorescent protein as an alternative control reporter to Renilla luciferase. Anal Biochem. 2005; 342(2):345-7. PMC: 1974853. DOI: 10.1016/j.ab.2005.04.047. View

Hamamori Y, Wu H, Sartorelli V, Kedes L . The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist. Mol Cell Biol. 1997; 17(11):6563-73. PMC: 232510. DOI: 10.1128/MCB.17.11.6563. View

Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hirohashi S . Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci U S A. 1995; 92(16):7416-9. PMC: 41350. DOI: 10.1073/pnas.92.16.7416. View

Verzi M, Anderson J, Dodou E, Kelly K, Greene S, North B . N-twist, an evolutionarily conserved bHLH protein expressed in the developing CNS, functions as a transcriptional inhibitor. Dev Biol. 2002; 249(1):174-90. DOI: 10.1006/dbio.2002.0753. View

10.

Wang S, Coljee V, Pignolo R, Rotenberg M, Cristofalo V, Sierra F . Cloning of the human twist gene: its expression is retained in adult mesodermally-derived tissues. Gene. 1997; 187(1):83-92. View

11.

Duriseti S, Winnard Jr P, Mironchik Y, Vesuna F, Raman A, Raman V . HOXA5 regulates hMLH1 expression in breast cancer cells. Neoplasia. 2006; 8(4):250-8. PMC: 1600677. DOI: 10.1593/neo.05766. View

12.

Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R . Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol. 2002; 161(5):1881-91. PMC: 1850763. DOI: 10.1016/S0002-9440(10)64464-1. View

13.

Murre C, McCaw P, Baltimore D . A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989; 56(5):777-83. DOI: 10.1016/0092-8674(89)90682-x. View

14.

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

15.

Perk J, Iavarone A, Benezra R . Id family of helix-loop-helix proteins in cancer. Nat Rev Cancer. 2005; 5(8):603-14. DOI: 10.1038/nrc1673. View

16.

Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J . The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000; 2(2):84-9. DOI: 10.1038/35000034. View

17.

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

18.

Bussemakers M, van Bokhoven A, Mees S, Kemler R, Schalken J . Molecular cloning and characterization of the human E-cadherin cDNA. Mol Biol Rep. 1993; 17(2):123-8. DOI: 10.1007/BF00996219. View

19.

Lee M, Lowe G, Strong D, Wergedal J, Glackin C . TWIST, a basic helix-loop-helix transcription factor, can regulate the human osteogenic lineage. J Cell Biochem. 1999; 75(4):566-77. DOI: 10.1002/(sici)1097-4644(19991215)75:4<566::aid-jcb3>3.0.co;2-0. View

20.

Ji X, Woodard A, Rimm D, Fearon E . Transcriptional defects underlie loss of E-cadherin expression in breast cancer. Cell Growth Differ. 1997; 8(7):773-8. View