Frequently rearranged and overexpressed δ-catenin is responsible for low sensitivity of prostate cancer cells to androgen receptor and β-catenin antagonists

Oncotarget
Piyan ZhangIrina V Kovtun

Abstract

The mechanism of prostate cancer (PCa) progression towards the hormone refractory state remains poorly understood. Treatment options for such patients are limited and present a major clinical challenge. Previously, δ-catenin was reported to promote PCa cell growth in vitro and its increased level is associated with PCa progression in vivo. In this study we show that re-arrangements at Catenin Delta 2 (CTNND2) locus, including gene duplications, are very common in clinically significant PCa and may underlie δ-catenin overexpression. We find that δ-catenin in PCa cells exists in a complex with E-cadherin, p120, and α- and β-catenin. Increased expression of δ-catenin leads to its further stabilization as well as upregulation and stabilization of its binding partners. Resistant to degradation and overexpressed δ-catenin isoform activates Wnt signaling pathway by increasing the level of nuclear β-catenin and subsequent stimulation of Tcf/Lef transcription targets. Evaluation of responses to treatments, with androgen receptor (AR) antagonist and β-catenin inhibitors revealed that cells with high levels of δ-catenin are more resistant to killing with single agent treatment than matched control cells. We show that combination treatment...Continue Reading

References

Jul 1, 1997·The EMBO Journal·H AberleR Kemler
Oct 6, 1997·The Journal of Biological Chemistry·K OrfordS W Byers
Apr 24, 1999·Genes & Development·R Bhatia-GaurM M Shen
Dec 26, 2001·EMBO Reports·Frank J T StaalHans C Clevers
Jan 17, 2002·The Journal of Biological Chemistry·Fajun YangZijie Sun
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Michelle Jane BurgerRobert Alexander Gardiner
Sep 12, 2002·EMBO Reports·Beric R Henderson, Francois Fagotto
Dec 4, 2003·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Michael M Shen, Cory Abate-Shen
Jul 30, 2004·Molecular and Cellular Biology·Marianna RodovaMichael J Werle
Jan 14, 2005·The Journal of Biological Chemistry·Jong In YookStephen J Weiss
Mar 1, 2005·Oncogene·Yin-Yuan MoWilliam T Beck
Jul 19, 2005·Cancer Letters·Meletios Verras, Zijie Sun
Sep 6, 2005·The Journal of Biological Chemistry·Liang-Nian Song, Edward P Gelmann
May 23, 2006·Current Biology : CB·Reto StädeliKonrad Basler
Aug 15, 2006·Biochimica Et Biophysica Acta·Stefano Alemà, Anna Maria Salvatore
Dec 19, 2006·Nature Genetics·Scott A TomlinsArul M Chinnaiyan
Jan 16, 2007·Science·Debdyuti Mukhopadhyay, Howard Riezman
Oct 25, 2007·International Journal of Urology : Official Journal of the Japanese Urological Association·Yong-Guang JiangYun-Hua Lin
Nov 15, 2007·Nature Reviews. Molecular Cell Biology·Ruth Geiss-Friedlander, Frauke Melchior
May 7, 2008·The Prostate·Hayley C WhitakerDavid E Neal
Jun 3, 2008·European Urology·George W YardyWalter F Bodmer
Jul 1, 2008·Biochemical and Biophysical Research Communications·Jie LuChangwen Jin
Aug 20, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John C ChevilleGeorge Vasmatzis
Nov 26, 2008·European Journal of Pharmacology·Wenyan LuYonghe Li
May 19, 2009·Nature Cell Biology·Shu-Ping WangPan-Chyr Yang
Feb 5, 2010·BMC Molecular Biology·Elisabetta LambertiniRoberta Piva

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
ubiquitination
sumoylation
laser capture microdissection
electrophoresis
immunoprecipitation
pull down
co-immunoprecipitation
transfection
transfect

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.