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

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Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases. / De Piano, Mario; Manuelli, Valeria; Zadra, Giorgia ; Otte, Jonathan; Edqvist, Per-Henrik; Ponten, Fredrik; Nowinski, Salpi; Niaouris, Athanasios; Grigoriadis, Anita; Loda, Massimo; Van Hemelrijck, Mieke; Wells, Claire M.

In: Oncogene, Vol. 39, No. 18, 30.04.2020, p. 3666–3679.

Research output: Contribution to journalArticle

Harvard

De Piano, M, Manuelli, V, Zadra, G, Otte, J, Edqvist, P-H, Ponten, F, Nowinski, S, Niaouris, A, Grigoriadis, A, Loda, M, Van Hemelrijck, M & Wells, CM 2020, 'Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases', Oncogene, vol. 39, no. 18, pp. 3666–3679. https://doi.org/10.1038/s41388-020-1243-2

APA

De Piano, M., Manuelli, V., Zadra, G., Otte, J., Edqvist, P-H., Ponten, F., ... Wells, C. M. (2020). Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases. Oncogene, 39(18), 3666–3679. https://doi.org/10.1038/s41388-020-1243-2

Vancouver

De Piano M, Manuelli V, Zadra G, Otte J, Edqvist P-H, Ponten F et al. Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases. Oncogene. 2020 Apr 30;39(18):3666–3679. https://doi.org/10.1038/s41388-020-1243-2

Author

De Piano, Mario ; Manuelli, Valeria ; Zadra, Giorgia ; Otte, Jonathan ; Edqvist, Per-Henrik ; Ponten, Fredrik ; Nowinski, Salpi ; Niaouris, Athanasios ; Grigoriadis, Anita ; Loda, Massimo ; Van Hemelrijck, Mieke ; Wells, Claire M. / Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases. In: Oncogene. 2020 ; Vol. 39, No. 18. pp. 3666–3679.

Bibtex Download

@article{dea0e35dd2694b6ca0c3b82bfed1c7b7,
title = "Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases",
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 migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.",
author = "{De Piano}, Mario and Valeria Manuelli and Giorgia Zadra and Jonathan Otte and Per-Henrik Edqvist and Fredrik Ponten and Salpi Nowinski and Athanasios Niaouris and Anita Grigoriadis and Massimo Loda and {Van Hemelrijck}, Mieke and Wells, {Claire M}",
year = "2020",
month = "4",
day = "30",
doi = "10.1038/s41388-020-1243-2",
language = "English",
volume = "39",
pages = "3666–3679",
journal = "Oncogene",
issn = "0950-9232",
number = "18",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

AU - De Piano, Mario

AU - Manuelli, Valeria

AU - Zadra, Giorgia

AU - Otte, Jonathan

AU - Edqvist, Per-Henrik

AU - Ponten, Fredrik

AU - Nowinski, Salpi

AU - Niaouris, Athanasios

AU - Grigoriadis, Anita

AU - Loda, Massimo

AU - Van Hemelrijck, Mieke

AU - Wells, Claire M

PY - 2020/4/30

Y1 - 2020/4/30

N2 - 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 migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

AB - 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 migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=85081556450&partnerID=8YFLogxK

U2 - 10.1038/s41388-020-1243-2

DO - 10.1038/s41388-020-1243-2

M3 - Article

VL - 39

SP - 3666

EP - 3679

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 18

ER -

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