alexa TGFβ-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells.
Reproductive Medicine

Reproductive Medicine

Gynecology & Obstetrics

Author(s): Mu Y, Zang G, Engstrm U, Busch C, Landstrm M

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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-Par6(345)-specific antibody and verified its specificity in vitro. Endogenous p-Par6(345) was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6(345) 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 aPKCζ. The p-Par6-aPKCζ 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-Par6Ser(345) levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.

This article was published in Br J Cancer. and referenced in Gynecology & Obstetrics

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