Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN-mutated prostate cancer cells

The Prostate
T OhigashiM Murai

Abstract

The cross-talk between Wnt signaling and the Akt pathway in prostate cancer (Pca) is still unclear. In the present study, we found that WIF-1 downregulates the Akt pathway and also enhances chemosensitivity in PTEN-null Pca cells. Wnt inhibitory factor-1 (WIF-1), an inhibitor of Wnt proteins, was transfected into PC-3 and DU145 Pca cells. Akt was phosphorylated in PTEN-null PC-3 cells but underphosphorylated in PTEN-expressed DU145 cells. The levels of phosphorylated Akt in WIF-1 overexpressing PC-3 cells were lower than those in native or control vector-transfected PC-3 cells. However, WIF-1 showed no additional inhibition of already reduced Akt activity in DU145 cells. Overexpression of WIF-1 resulted in sensitizing PC-3 cells for paclitaxel to induce apoptosis. DU145 cells were more sensitive to paclitaxel but were not affected by WIF-1 transfection. The PI3K inhibitor LY294002 seemed to restore the chemosensitivity of native PC-3 cells like WIF-1 did. Our results show that Wnt signaling is involved in Akt activation in Pca cells. Our data also indicate the possibility that Wnt and its signaling pathway can be therapeutic targets for PTEN-mutated advanced Pca.

References

Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Oct 13, 1994·The New England Journal of Medicine·W J Catalona
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·M AndjelkovićB A Hemmings
Jun 7, 1997·Biochimica Et Biophysica Acta·P Polakis
Feb 7, 1998·Genes & Development·K M Cadigan, R Nusse
Feb 28, 1998·The Biochemical Journal·T C Dale
Apr 30, 1998·Current Opinion in Cell Biology·J D Brown, R T Moon
Nov 13, 1998·Science·M H CardoneJ C Reed
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·D PennicaA J Levine
Mar 30, 2001·The Journal of Biological Chemistry·S FukumotoM E Lee
Jul 20, 2001·The Journal of Biological Chemistry·H ThakkarR K Srivastava
Aug 10, 2001·The Journal of Biological Chemistry·H HuangD J Tindall
May 1, 2002·The Journal of Cell Biology·Zongbing YouCun-Yu Wang
Jun 28, 2002·The Journal of Biological Chemistry·Seiji MabuchiYuji Murata
Jul 26, 2002·Molecular and Cellular Biology·Lawrence P KaneArthur Weiss
Aug 3, 2002·The Journal of Biological Chemistry·Kenneth A LongoOrmond A MacDougald
Jan 10, 2004·Endocrine-related Cancer·D R Chesire, W B Isaacs

❮ Previous
Next ❯

Citations

Sep 29, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Maisa YoshimotoAndrew J Evans
Dec 22, 2012·Nature Reviews. Cancer·Jamie N Anastas, Randall T Moon
Jun 20, 2012·Nature Reviews. Urology·Robert M Kypta, Jonathan Waxman
Jul 24, 2013·Briefings in Functional Genomics·Bryan D HudsonGabriela G Loots
Sep 7, 2005·Pathology International·Noboru KonishiMitsutoshi Nakamura
May 17, 2007·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·P AthanassiadouE Patsouris
Oct 1, 2009·Epigenomics·Francesco CreaWilliam L Farrar
May 3, 2011·Trends in Pharmacological Sciences·Francesco CreaRomano Danesi
Jan 2, 2008·Biochimica Et Biophysica Acta·A M JoshuaJ A Squire
Feb 9, 2007·Cancer Letters·Jane Bayani, Jeremy A Squire
Mar 19, 2015·Scientific Reports·Huayue LinZhong-Ying Zhang
Apr 27, 2011·Annals of Neurology·David KremerPatrick Küry
Feb 16, 2006·Journal of Molecular Biology·Edvards LiepinshGottfried Otting
Mar 7, 2006·Biochemical and Biophysical Research Communications·Sonny BatraDavid M Jablons
Jul 19, 2005·Cancer Letters·Meletios Verras, Zijie Sun
Mar 3, 2015·The Prostate·Berna UygurWen-Shu Wu
Aug 17, 2016·BioMed Research International·Long LiHong-Zhang Huang
Jan 1, 2011·Cancers·Kenneth C ValkenburgBart O Williams
Sep 8, 2018·Journal of Cellular Physiology·Mehran PashirzadSeyed Mahdi Hassanian
Apr 20, 2016·Molecular and Cellular Biology·Ion CristóbalJesús García-Foncillas
May 1, 2008·Head & Neck·Josephine ChouDavid M Jablons

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis