2005
DOI: 10.1158/0008-5472.can-05-0060
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E1AF/PEA3 Activates the Rho/Rho-Associated Kinase Pathway to Increase the Malignancy Potential of Non–Small-Cell Lung Cancer Cells

Abstract: E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non-small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rhoassociated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, w… Show more

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Cited by 45 publications
(33 citation statements)
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“…RhoA activation is linked to the formation of focal adhesion complexes and actin stress fibers (9), while Rac1 and Cdc42 are associated with lamellipodia and filopodia formation, respectively. A recent investigation into Rho in lung cancers found that E1AF/PEA3, an Ets family transcription factor is often overexpressed in non-small cell lung carcinomas, activates the Rho/ROCK signaling pathway, lending to increased cell motility and metastasis (10). Also, a separate study utilized siRNA against the Rho proteins Rac1 and Rac2, and demonstrated that blocking the activity of Rac resulted in inhibition of lamellipodia, migration, and invasion of glioma and breast carcinoma cells (11).…”
Section: Discussionmentioning
confidence: 99%
“…RhoA activation is linked to the formation of focal adhesion complexes and actin stress fibers (9), while Rac1 and Cdc42 are associated with lamellipodia and filopodia formation, respectively. A recent investigation into Rho in lung cancers found that E1AF/PEA3, an Ets family transcription factor is often overexpressed in non-small cell lung carcinomas, activates the Rho/ROCK signaling pathway, lending to increased cell motility and metastasis (10). Also, a separate study utilized siRNA against the Rho proteins Rac1 and Rac2, and demonstrated that blocking the activity of Rac resulted in inhibition of lamellipodia, migration, and invasion of glioma and breast carcinoma cells (11).…”
Section: Discussionmentioning
confidence: 99%
“…To determine inducibility of TAM67 expression in tumours, mice were killed 7 days after the randomisation and local skin tumours were removed. Protein was extracted from the tumours and subjected to western blot analysis as described previously (Hakuma et al, 2005). The animal studies conducted have been approved by the Institutional Ethical Board for animal welfare at the Hokkaido University Graduate School of Medicine.…”
Section: Nude Mouse Xenograft Experimentsmentioning
confidence: 99%
“…Rho also plays a positive role in the regulation of cell motility. Indeed, the inhibition of Rho, through the microinjection of the Rho inhibitor, Clostridium botulinum ADP-ribosyltransferase C3 (C3T), inhibits cell motility in many cell systems [8,9]. Initially, the role of RhoA during cell motility was thought to be restricted to the generation of contractile force and focal adhesion turnover needed for tail retraction [10,11].…”
Section: Introductionmentioning
confidence: 99%