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

British Journal of Cancer
Y MuMarene Landström

Abstract

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. 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. 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 corr...Continue Reading

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Citations

Jul 16, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hifzur R SiddiqueKeigo Machida
May 2, 2019·Biomedical Chromatography : BMC·Munazza Raza MirzaGünther K Bonn
Jun 8, 2017·Clinical and Experimental Pharmacology & Physiology·Lingling RuanHanqing Liu
Jul 12, 2018·Journal of Molecular Histology·Kun YuHua Yang
Jan 30, 2018·Expert Review of Proteomics·Camilla ThygesenMartin R Larsen
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei LiuXiaojun Yang

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Methods Mentioned

BETA
GTPases
GTPase
Assay
nuclear translocation

Software Mentioned

ImageJ
SPSS
QED

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