title: The involvement of mutant Rac1 in the formation of invadopodia in cultured melanoma cells.
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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Or-Yam
authors.initials: OY
authors.lastname: Revach
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Sabina E
authors.initials: SE
authors.lastname: Winograd-Katz
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: benny.geiger@weizmann.ac.il.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D008545:Melanoma / Q000503:physiopathology*; D009154:Mutation; D000069261:Podosomes / Q000473:pathology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
chemical_list: D020830:rac1 GTP-Binding Protein
keywords: Cell adhesion; Cell invasion; Cellular mechanics; Invadopodia; Melanoma; Metastasis; Rac1