FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma

Summary: Despite the undisputable role of the small GTPase Rac1 in the regulation of actin cytoskeleton reorganization, the Rac guanine-nucleotide exchange factors (Rac-GEFs) involved in Rac1-mediated motility and invasion in human lung adenocarcinoma cells remain largely unknown. Here, we identify...

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Autores principales:	Mariana Cooke, Gabriel Kreider-Letterman, Martin J. Baker, Suli Zhang, Neil T. Sullivan, Evgeniy Eruslanov, Martin C. Abba, Silvia M. Goicoechea, Rafael García-Mata, Marcelo G. Kazanietz
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Rac1 Rac-GEF EGFR lung cancer AXL FARP1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/224c07e16fe044f2b5b738435738af84
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spelling	oai:doaj.org-article:224c07e16fe044f2b5b738435738af842021-11-04T04:28:53ZFARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma2211-124710.1016/j.celrep.2021.109905https://doaj.org/article/224c07e16fe044f2b5b738435738af842021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013759https://doaj.org/toc/2211-1247Summary: Despite the undisputable role of the small GTPase Rac1 in the regulation of actin cytoskeleton reorganization, the Rac guanine-nucleotide exchange factors (Rac-GEFs) involved in Rac1-mediated motility and invasion in human lung adenocarcinoma cells remain largely unknown. Here, we identify FARP1, ARHGEF39, and TIAM2 as essential Rac-GEFs responsible for Rac1-mediated lung cancer cell migration upon EGFR and c-Met activation. Noteworthily, these Rac-GEFs operate in a non-redundant manner by controlling distinctive aspects of ruffle dynamics formation. Mechanistic analysis reveals a leading role of the AXL-Gab1-PI3K axis in conferring pro-motility traits downstream of EGFR. Along with the positive association between the overexpression of Rac-GEFs and poor lung adenocarcinoma patient survival, we show that FARP1 and ARHGEF39 are upregulated in EpCam+ cells sorted from primary human lung adenocarcinomas. Overall, our study reveals fundamental insights into the complex intricacies underlying Rac-GEF-mediated cancer cell motility signaling, hence underscoring promising targets for metastatic lung cancer therapy.Mariana CookeGabriel Kreider-LettermanMartin J. BakerSuli ZhangNeil T. SullivanEvgeniy EruslanovMartin C. AbbaSilvia M. GoicoecheaRafael García-MataMarcelo G. KazanietzElsevierarticleRac1Rac-GEFEGFRlung cancerAXLFARP1Biology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109905- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Rac1 Rac-GEF EGFR lung cancer AXL FARP1 Biology (General) QH301-705.5
spellingShingle	Rac1 Rac-GEF EGFR lung cancer AXL FARP1 Biology (General) QH301-705.5 Mariana Cooke Gabriel Kreider-Letterman Martin J. Baker Suli Zhang Neil T. Sullivan Evgeniy Eruslanov Martin C. Abba Silvia M. Goicoechea Rafael García-Mata Marcelo G. Kazanietz FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma
description	Summary: Despite the undisputable role of the small GTPase Rac1 in the regulation of actin cytoskeleton reorganization, the Rac guanine-nucleotide exchange factors (Rac-GEFs) involved in Rac1-mediated motility and invasion in human lung adenocarcinoma cells remain largely unknown. Here, we identify FARP1, ARHGEF39, and TIAM2 as essential Rac-GEFs responsible for Rac1-mediated lung cancer cell migration upon EGFR and c-Met activation. Noteworthily, these Rac-GEFs operate in a non-redundant manner by controlling distinctive aspects of ruffle dynamics formation. Mechanistic analysis reveals a leading role of the AXL-Gab1-PI3K axis in conferring pro-motility traits downstream of EGFR. Along with the positive association between the overexpression of Rac-GEFs and poor lung adenocarcinoma patient survival, we show that FARP1 and ARHGEF39 are upregulated in EpCam+ cells sorted from primary human lung adenocarcinomas. Overall, our study reveals fundamental insights into the complex intricacies underlying Rac-GEF-mediated cancer cell motility signaling, hence underscoring promising targets for metastatic lung cancer therapy.
format	article
author	Mariana Cooke Gabriel Kreider-Letterman Martin J. Baker Suli Zhang Neil T. Sullivan Evgeniy Eruslanov Martin C. Abba Silvia M. Goicoechea Rafael García-Mata Marcelo G. Kazanietz
author_facet	Mariana Cooke Gabriel Kreider-Letterman Martin J. Baker Suli Zhang Neil T. Sullivan Evgeniy Eruslanov Martin C. Abba Silvia M. Goicoechea Rafael García-Mata Marcelo G. Kazanietz
author_sort	Mariana Cooke
title	FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma
title_short	FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma
title_full	FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma
title_fullStr	FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma
title_full_unstemmed	FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma
title_sort	farp1, arhgef39, and tiam2 are essential receptor tyrosine kinase effectors for rac1-dependent cell motility in human lung adenocarcinoma
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/224c07e16fe044f2b5b738435738af84
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FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma

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