上海科技大学知识管理系统

Despite a lack of mutations, accumulating evidence supports an important role for the Wnt/βcatenin pathway in ovarian tumorigenesis. However, the molecular mechanism that contributes to the aberrant activation of the Wnt signaling cascade in ovarian cancer has not been fully elucidated. Here, we found that protein tyrosine phosphatase receptor type R (PTPRR) suppressed the activation of the Wnt/βcatenin pathway in ovarian cancer. We performed an shRNA-based biochemical screen, which identified PTPRR as being responsible for tyrosine dephosphorylation of βcatenin on Tyr-142, a key site controlling the transcriptional activity of βcatenin. Of note, PTPRR was down-regulated in ovarian cancers, and ectopic PTPRR re-expression delayed ovarian cancer cell growth both in vitro and in vivo. Using a proximity-based tagging system and RNA-Seq analysis, we identified a signaling nexus that includes PTPRR, βcatenin, βcatenin, E-cadherin, and AT-rich interaction domain 3C (ARID3C) in ovarian cancer. Immunohistochemistry staining of human samples further suggested that PTPRR expression is inversely correlated with disease prognosis. Collectively, our findings indicate that PTPRR functions as a tumor suppressor in ovarian cancer by dephosphorylating and inactivatingβcatenin. These results suggest that PTPRR expression might have utility as a prognostic marker for predicting overall survival.
© 2019 Wang et al.