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PMID: 26873115 Published · ppublish English Journal Article Review Research Support, Non-U.S. Gov't

The involvement of mutant Rac1 in the formation of invadopodia in cultured melanoma cells.

Experimental cell research ·Vol. 343 ·No. 1 ·2016-00-10 ·Pages 82-88

Revach OY, Winograd-Katz SE, Samuels Y, Geiger B

Abstract

In this article, we discuss the complex involvement of a Rho-family GTPase, Rac1, in cell migration and in invadopodia-mediated matrix degradation. We discuss the involvement of invadopodia in invasive cell migration, and their capacity to promote cancer metastasis. Considering the regulation of invadopodia formation, we describe studies that demonstrate the role of Rac1 in the metastatic process, and the suggestion that this effect is attributable to the capacity of Rac1 to promote invadopodia formation. This notion is demonstrated here by showing that knockdown of Rac1 in melanoma cells expressing a wild-type form of this GTPase, reduces invadopodia-dependent matrix degradation. Interestingly, we also show that excessive activity of Rac1, displayed by the P29S, hyperactive, "fast cycling" mutant of Rac1, which is present in 5-10% of melanoma tumors, inhibits invadopodia function. Moreover, knockdown of this hyperactive mutant enhanced matrix degradation, indicating that excessive Rac1 activity by this mutant can negatively regulate invadopodia formation and function.

Keywords
Cell adhesion Cell invasion Cellular mechanics Invadopodia Melanoma Metastasis Rac1
MeSH Terms
Blotting, Western Cell Line, Tumor Cell Movement Cells, Cultured Humans Melanoma/physiopathology Mutation Podosomes/pathology rac1 GTP-Binding Protein/genetics
Chemicals
rac1 GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Revach Or-Yam
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Winograd-Katz Sabina E
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Samuels Yardena
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Geiger Benjamin
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: benny.geiger@weizmann.ac.il.
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Article Info
Journal
Experimental cell research
Abbr.
Exp Cell Res
ISSN
1090-2422
DOI
10.1016/j.yexcr.2016.02.003
Email
benny.geiger@weizmann.ac.il
Published
2016-00-10
Epub
2016-00-10
Pages
82-88
Language
English
Region
United States
NLM ID
0373226
PMCID
PMC4954600
Subset
IM
Grants
European Research Council · 335377 · International
External Links
PubMed source DOI: 10.1016/j.yexcr.2016.02.003 PMC Full Text View journal details
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