SGK1-dependent intestinal tumor growth in APC-deficient mice

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Kan WangFlorian Lang

Abstract

Adenomatous polyposis coli (APC) is inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying defective APC (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC binds GSK3beta, which phosphorylates beta-catenin thus fostering its degradation. beta-catenin upregulates the serum- and glucocorticoid-inducible kinase Sgk1, which inhibits GSK3beta. The present study explored the role of SGK1 in tumor growth of apc(Min/+)mice. apc(Min/+)mice were crossed with SGK1-knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) generating apc(Min/+)/sgk1(-/-)mice and apc(Min/+)/sgk1(+/+)mice. beta-catenin abundance was determined by Western blotting and confocal microscopy. As a result apc(Min/+)/sgk1(+/+)mice developed significantly more intestinal tumors than apc(Min/+)/sgk1(-/-)mice. Following chemical cancerogenesis, colonic beta-catenin protein abundance was significantly higher in sgk1(+/+)mice than in sgk1(-/-)mice. beta-catenin expression was significantly increased in HEK293 cells treated with dexamethasone for upregulation of Sgk1. In conclusion, SGK1 expression favors the development of intestinal tumors in APC-deficient mice, an effect at least partially due to enhanced be...Continue Reading

Citations

Apr 9, 2011·Pflügers Archiv : European journal of physiology·Rexhep RexhepajFlorian Lang
Apr 2, 2014·Journal of Theoretical Biology·Joanna KawkaAnna Marciniak-Czochra
Apr 8, 2015·International Journal of Molecular Sciences·Rebeca González-FernándezPablo Martín-Vasallo
Jun 12, 2012·Cell Calcium·Florian LangEkaterina Shumilina
Dec 3, 2014·Biochimica Et Biophysica Acta·Kai XuWenyi Wei
Jun 15, 2010·The International Journal of Biochemistry & Cell Biology·Florian LangChristos Stournaras
Nov 25, 2017·Experimental & Molecular Medicine·Xuchun LiangJunjie Xiao
Sep 27, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Florian Lang, Ekaterina Shumilina
Mar 10, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anja EylensteinFlorian Lang
Oct 17, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lennard Y W LeeIan Tomlinson
Feb 6, 2021·Frontiers in Oncology·Yiwen SangWeiwei Liu

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