TGFβ-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells

30Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: The Par complex - comprising partition-defective 6 (Par6), Par3, and atypical protein kinase C (aPKC) - is crucial for cell polarisation, the loss of which contributes to cancer progression. Transforming growth factor β (TGFβ)-induced phosphorylation of Par6 on the conserved serine 345 is implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here we investigated the importance of phosphorylated Par6 in prostate cancer. Methods: We generated a p-Par6345-specific antibody and verified its specificity in vitro. Endogenous p-Par6345 was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6345 in migrating TGFβ-treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGFβ-treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues. Results: TGFβ induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKCz. The p-Par6-aPKCz complex is important for cell migration and invasion, as interference with this complex prevented prostate cancer cell invasion. High levels of activated Par6 correlated with aggressive prostate cancer. Conclusions: Increased p-Par6Ser345 levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.

Cite

CITATION STYLE

APA

Mu, Y., Zang, G., Engström, U., Busch, C., & Landström, M. (2015). TGFβ-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells. British Journal of Cancer, 112(7), 1223–1231. https://doi.org/10.1038/bjc.2015.71

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free