Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases.

Oncogene
Mario De PianoClaire M Wells

Abstract

Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell mi...Continue Reading

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Citations

Oct 13, 2020·Small GTPases·Mario De PianoClaire M Wells
Nov 10, 2020·The Journal of Pathology·Débora C BastosMassimo Loda
Jul 28, 2020·Advanced Drug Delivery Reviews·Lisa M ButlerJohannes V Swinnen
Jan 12, 2021·Molecular Oncology·Soazik P JaminMichael Primig
Jun 20, 2021·Cancer Research·Laura A Sena, Samuel R Denmeade

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Methods Mentioned

BETA
GTPases
transfection
GTPase
PCR
FCS
immunoprecipitation
electrophoresis
RNAseq

Software Mentioned

Pro Plus
ImageJ
RNAseq
Image
Mathematica

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