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TGF beta-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2015 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 7, 1223-1231 p.Article in journal (Refereed) Published
Abstract [en]


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 beta (TGF beta)-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.


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 TGF beta-treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGF beta-treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues.


TGF beta 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 aPKC zeta. The p-Par6-aPKC zeta 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.

Place, publisher, year, edition, pages
2015. Vol. 112, no 7, 1223-1231 p.
Keyword [en]
Invasion, migration, Par6, prostate cancer, TGFβ
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-103553DOI: 10.1038/bjc.2015.71ISI: 000352145300010PubMedID: 25756394OAI: diva2:813829
Available from: 2015-05-25 Created: 2015-05-21 Last updated: 2015-12-01Bibliographically approved

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