Repression of PTEN Phosphatase by Snail1 Transcriptional Factor During Gamma Radiation-induced Apoptosis

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2008 Jan 4

PMID 18172008

Citations 99

Authors

Maria Escriva

Sandra Peiro

Nicolas Herranz

Patricia Villagrasa

Natalia Dave

Barbara Montserrat-Sentis

Stephen A Murray

Clara Franci

Thomas Gridley

Ismo Virtanen

Antonio Garcia de Herreros

Affiliations

Soon will be listed here.

Abstract

The product of the Snail1 gene is a transcriptional repressor required for triggering the epithelial-to-mesenchymal transition. Furthermore, ectopic expression of Snail1 in epithelial cells promotes resistance to apoptosis. In this study, we demonstrate that this resistance to gamma radiation-induced apoptosis caused by Snail1 is associated with the inhibition of PTEN phosphatase. In MDCK cells, mRNA levels of the p53 target gene PTEN are induced after gamma radiation; the transfection of Snail1 prevents this up-regulation. Decreased mRNA levels of PTEN were also detected in RWP-1 cells after the ectopic expression of this transcriptional factor. Snail1 represses and associates to the PTEN promoter as detected both by the electrophoretic mobility shift assay and chromatin immunoprecipitation experiments performed with either endogenous or ectopic Snail1. The binding of Snail1 to the PTEN promoter increases after gamma radiation, correlating with the stabilization of Snail1 protein, and prevents the association of p53 to the PTEN promoter. These results stress the critical role of Snail1 in the control of apoptosis and demonstrate the regulation of PTEN phosphatase by this transcriptional repressor.

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References

Savagner P . Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays. 2001; 23(10):912-23. DOI: 10.1002/bies.1132. View

Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, VAN Roy F . Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene. 2007; 26(53):7445-56. DOI: 10.1038/sj.onc.1210546. View

Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E . Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem. 2002; 277(42):39209-16. DOI: 10.1074/jbc.M206400200. View

Inoue A, Seidel M, Wu W, Kamizono S, Ferrando A, Bronson R . Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo. Cancer Cell. 2002; 2(4):279-88. DOI: 10.1016/s1535-6108(02)00155-1. View

Roig J, Traugh J . p21-activated protein kinase gamma-PAK is activated by ionizing radiation and other DNA-damaging agents. Similarities and differences to alpha-PAK. J Biol Chem. 1999; 274(44):31119-22. DOI: 10.1074/jbc.274.44.31119. View

Cano A, Perez-Moreno M, Rodrigo I, Locascio A, Blanco M, del Barrio M . The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000; 2(2):76-83. DOI: 10.1038/35000025. View

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

Liliental J, Moon S, Lesche R, Mamillapalli R, Li D, Zheng Y . Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr Biol. 2001; 10(7):401-4. DOI: 10.1016/s0960-9822(00)00417-6. View

Zhou X, Gimm O, Hampel H, Niemann T, Walker M, Eng C . Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am J Pathol. 2000; 157(4):1123-8. PMC: 1850161. DOI: 10.1016/S0002-9440(10)64627-5. View

10.

Freeman M . Feedback control of intercellular signalling in development. Nature. 2000; 408(6810):313-9. DOI: 10.1038/35042500. View

11.

Salvesen H, Macdonald N, Ryan A, Jacobs I, Lynch E, Akslen L . PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int J Cancer. 2001; 91(1):22-6. DOI: 10.1002/1097-0215(20010101)91:1<22::aid-ijc1002>3.0.co;2-s. View

12.

Simpson L, Parsons R . PTEN: life as a tumor suppressor. Exp Cell Res. 2001; 264(1):29-41. DOI: 10.1006/excr.2000.5130. View

13.

Stambolic V, Macpherson D, Sas D, Lin Y, Snow B, Jang Y . Regulation of PTEN transcription by p53. Mol Cell. 2001; 8(2):317-25. DOI: 10.1016/s1097-2765(01)00323-9. View

14.

Yamada K, Araki M . Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 2001; 114(Pt 13):2375-82. DOI: 10.1242/jcs.114.13.2375. View

15.

Bolos V, Peinado H, Perez-Moreno M, Fraga M, Esteller M, Cano A . The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci. 2003; 116(Pt 3):499-511. DOI: 10.1242/jcs.00224. View

16.

Ikenouchi J, Matsuda M, Furuse M, Tsukita S . Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci. 2003; 116(Pt 10):1959-67. DOI: 10.1242/jcs.00389. View

17.

Grille S, Bellacosa A, Upson J, Klein-Szanto A, van Roy F, Lee-Kwon W . The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 2003; 63(9):2172-8. View

18.

Peinado H, Quintanilla M, Cano A . Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J Biol Chem. 2003; 278(23):21113-23. DOI: 10.1074/jbc.M211304200. View

19.

Dominguez D, Montserrat-Sentis B, Virgos-Soler A, Guaita S, Grueso J, Porta M . Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor. Mol Cell Biol. 2003; 23(14):5078-89. PMC: 162233. DOI: 10.1128/MCB.23.14.5078-5089.2003. View

20.

Taki M, Kamata N, Yokoyama K, Fujimoto R, Tsutsumi S, Nagayama M . Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells. Cancer Sci. 2003; 94(7):593-7. PMC: 11160266. DOI: 10.1111/j.1349-7006.2003.tb01488.x. View