A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via FAK signaling

Rajinder S. Sawhney, Wensheng Liu, Michael G. Brattain

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

In metastatic cancer, high expression levels of vitronectin (VN) receptors (integrins), FAK, and ERK5are reported. We hypothesized that integrin-mediated ERK5 activation via FAK may play a pivotal role in cell adhesion, motility, and metastasis. ERK5 and FAK phosphorylation when metastatic MDA-MB-231 and PC-3 cells were plated on VN was enhanced. Further experiments showed co-immunoprecipitation of integrins β1, αVβ3, or aVb5 with ERK5 and FAK. To gain better insight into the mechanism of ERK5, FAK, and VN receptors in cell adhesion and motility, we performed loss-of-function experiments using integrin blocking antibodies, and specific mutants of FAK and ERK5. Ectopic expression of dominant negative ERK5/AEF decreased ERK5 and FAK (Y397) phosphorylation, cell adhesion, and haptotactic motility (micromotion) on VN. Additionally, DN FAK expression attenuated ERK5 phosphorylation, cell adhesion, and motility. This study documents the novel finding that in breast and prostate cancer cells, ERK5 is a critical target of FAK in cell adhesion signaling. Using different cancer cells, our experiments unveil a novel mechanism by which VN receptors and FAK could promote cancer metastasis via ERK5 activation. J. Cell. Physiol. 219: 152-161,2009.

Original languageEnglish (US)
Pages (from-to)152-161
Number of pages10
JournalJournal of Cellular Physiology
Volume219
Issue number1
DOIs
StatePublished - Apr 1 2009

Fingerprint

Cell adhesion
Vitronectin Receptors
Cell Adhesion
Integrins
Cell Movement
Cells
Phosphorylation
Vitronectin
Neoplasms
Chemical activation
Neoplasm Metastasis
Blocking Antibodies
Experiments
Immunoprecipitation
Prostatic Neoplasms
Breast Neoplasms

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via FAK signaling. / Sawhney, Rajinder S.; Liu, Wensheng; Brattain, Michael G.

In: Journal of Cellular Physiology, Vol. 219, No. 1, 01.04.2009, p. 152-161.

Research output: Contribution to journalArticle

Sawhney, Rajinder S. ; Liu, Wensheng ; Brattain, Michael G. / A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via FAK signaling. In: Journal of Cellular Physiology. 2009 ; Vol. 219, No. 1. pp. 152-161.
@article{5c07750ea4154c2b8ec39b64420b339e,
title = "A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via FAK signaling",
abstract = "In metastatic cancer, high expression levels of vitronectin (VN) receptors (integrins), FAK, and ERK5are reported. We hypothesized that integrin-mediated ERK5 activation via FAK may play a pivotal role in cell adhesion, motility, and metastasis. ERK5 and FAK phosphorylation when metastatic MDA-MB-231 and PC-3 cells were plated on VN was enhanced. Further experiments showed co-immunoprecipitation of integrins β1, αVβ3, or aVb5 with ERK5 and FAK. To gain better insight into the mechanism of ERK5, FAK, and VN receptors in cell adhesion and motility, we performed loss-of-function experiments using integrin blocking antibodies, and specific mutants of FAK and ERK5. Ectopic expression of dominant negative ERK5/AEF decreased ERK5 and FAK (Y397) phosphorylation, cell adhesion, and haptotactic motility (micromotion) on VN. Additionally, DN FAK expression attenuated ERK5 phosphorylation, cell adhesion, and motility. This study documents the novel finding that in breast and prostate cancer cells, ERK5 is a critical target of FAK in cell adhesion signaling. Using different cancer cells, our experiments unveil a novel mechanism by which VN receptors and FAK could promote cancer metastasis via ERK5 activation. J. Cell. Physiol. 219: 152-161,2009.",
author = "Sawhney, {Rajinder S.} and Wensheng Liu and Brattain, {Michael G.}",
year = "2009",
month = "4",
day = "1",
doi = "10.1002/jcp.21662",
language = "English (US)",
volume = "219",
pages = "152--161",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via FAK signaling

AU - Sawhney, Rajinder S.

AU - Liu, Wensheng

AU - Brattain, Michael G.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - In metastatic cancer, high expression levels of vitronectin (VN) receptors (integrins), FAK, and ERK5are reported. We hypothesized that integrin-mediated ERK5 activation via FAK may play a pivotal role in cell adhesion, motility, and metastasis. ERK5 and FAK phosphorylation when metastatic MDA-MB-231 and PC-3 cells were plated on VN was enhanced. Further experiments showed co-immunoprecipitation of integrins β1, αVβ3, or aVb5 with ERK5 and FAK. To gain better insight into the mechanism of ERK5, FAK, and VN receptors in cell adhesion and motility, we performed loss-of-function experiments using integrin blocking antibodies, and specific mutants of FAK and ERK5. Ectopic expression of dominant negative ERK5/AEF decreased ERK5 and FAK (Y397) phosphorylation, cell adhesion, and haptotactic motility (micromotion) on VN. Additionally, DN FAK expression attenuated ERK5 phosphorylation, cell adhesion, and motility. This study documents the novel finding that in breast and prostate cancer cells, ERK5 is a critical target of FAK in cell adhesion signaling. Using different cancer cells, our experiments unveil a novel mechanism by which VN receptors and FAK could promote cancer metastasis via ERK5 activation. J. Cell. Physiol. 219: 152-161,2009.

AB - In metastatic cancer, high expression levels of vitronectin (VN) receptors (integrins), FAK, and ERK5are reported. We hypothesized that integrin-mediated ERK5 activation via FAK may play a pivotal role in cell adhesion, motility, and metastasis. ERK5 and FAK phosphorylation when metastatic MDA-MB-231 and PC-3 cells were plated on VN was enhanced. Further experiments showed co-immunoprecipitation of integrins β1, αVβ3, or aVb5 with ERK5 and FAK. To gain better insight into the mechanism of ERK5, FAK, and VN receptors in cell adhesion and motility, we performed loss-of-function experiments using integrin blocking antibodies, and specific mutants of FAK and ERK5. Ectopic expression of dominant negative ERK5/AEF decreased ERK5 and FAK (Y397) phosphorylation, cell adhesion, and haptotactic motility (micromotion) on VN. Additionally, DN FAK expression attenuated ERK5 phosphorylation, cell adhesion, and motility. This study documents the novel finding that in breast and prostate cancer cells, ERK5 is a critical target of FAK in cell adhesion signaling. Using different cancer cells, our experiments unveil a novel mechanism by which VN receptors and FAK could promote cancer metastasis via ERK5 activation. J. Cell. Physiol. 219: 152-161,2009.

UR - http://www.scopus.com/inward/record.url?scp=60849093481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60849093481&partnerID=8YFLogxK

U2 - 10.1002/jcp.21662

DO - 10.1002/jcp.21662

M3 - Article

C2 - 19089993

AN - SCOPUS:60849093481

VL - 219

SP - 152

EP - 161

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 1

ER -