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


The cover for issue 36 of Oncotarget features Figure 4C, "A cartoon depicts binding complex of catenin proteins and E-cadherin in LNCaP cells, proposed on pull down experiments," from Zhang, et al.

The research shows that δ-catenin in PCa induces β-catenin which, in turn, impacts responses to existing androgen deprivation therapy and currently under development beta-catenin inhibitors.

Dr. Irina V. Kovtun said "Collectively our data suggest that PCa cells with overstimulated δ‐catenin/β-catenin network are resistant to androgen deprivation and β-catenin inhibition. Combination therapy targeting both pathways simultaneously may be considered for PCa with high levels of δ-catenin."

The ability of δ-catenin to activate Wnt/β-catenin signaling pathway in PCa poses a question whether β-catenin is a potential therapeutic target for PCa. In a cell model overexpressing δ-catenin we found that it stimulates levels of its binding partners E-cadherin, p120, and β-catenin and downstream targets of Tcf/Lef transcription factor.

In LNCaP cells ectopically expressing δ-catenin, only the higher molecular weight form of δ-catenin protein was detected.

Collectively their data suggest that PCa cells with overstimulated δ‐catenin/ β‐catenin network are resistant to androgen deprivation and β-catenin inhibition administered separately.

The Kovtun research team concluded that "targeting clinically significant PCa with high levels of δ‐catenin with anti‐androgen and anti β-catenin combination therapy may prevent progression of the disease to a castration-resistant state and, thus, represents a promising therapeutic strategy."

Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=25319&path%5B%5D=79321

Correspondence to - Irina V. Kovtun - Kovtun.Irina@mayo.edu

Keywords - delta catenin, prostate cancer, treatment, disease progression

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