Accession Number ADA570540
Title Autophagy Signaling in Prostate Cancer: Identification of a Novel Phosphatase.
Publication Date Jan 2013
Media Count 72p
Personal Author J. P. MacKeigan
Abstract Phosphatidylinositol-3-phosphate (PI(3)P) is concentrated on endocytic and autophagic vesicles and recruits effector proteins critical for these processes. In an effort to understand the phosphatase regulation of PI(3)P, we performed an RNA interference (RNAi) screen and found that knockdown of PTPRS (PTPsigma), a dual-domain protein tyrosine phosphatase (PTP), increases cellular PI(3)P and hyperactivates both constitutive and induced autophagy. We have found that PTPsigma localizes to PI(3)P-positive membranes in cells and its vesicular localization is enhanced during autophagy. Furthermore, PTPsigma is proteolytically processed from its location at the cell surface into a membrane-bound C-terminal fragment, which appears to be targeted to the lysosome. Taken together, our findings propose a novel role for PTPsigma and provide insight into the regulation of PI(3)P and autophagy. Intriguingly, we have previously demonstrated that RNAi-mediated knockdown of PTPsigma confers chemoresistance to cancer cells in culture. In addition, reduced expression of PTPsigma was found during the progression from primary prostate cancer to metastatic disease. Accordingly, our central hypothesis is that autophagy is activated in the absence of PTPsigma as a mechanism of chemoresistance, thereby densensitizing prostate cancer cells to chemotherapeutic stress and supporting disease progression.
Keywords Autophagy
Culture
Lipids
Phosphatases
Prostate cancer
Signals


 
Source Agency Non Paid ADAS
NTIS Subject Category 57A - Anatomy
57S - Physiology
57E - Clinical Medicine
Corporate Author Van Andel Research Institute, Grand Rapids, MI.
Document Type Technical report
Title Note Final rept. 23 Jul 2009-22 Jan 2013.
NTIS Issue Number 1315
Contract Number W81XWH-09-1-0528

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