Rac signaling in tumorigenesis and as target for anticancer drug development.
Rac GTPases are crucial signaling regulators in eukaryotic cells, acting downstream of many cell surface receptors. They play essential roles in diverse cellular functions including cytoskeleton dynamics, cell motility, cell survival and apoptosis. Their activities are controlled by a tightly regulated GDP/GTP cycle coupled with an alternation between cytoplasm and membrane compartments. Aberrant Rac signaling is found in some human cancers as a result of changes in the GTPase itself or in its regulation loops. This review highlights recent findings regarding the molecular and functional aspects of Rac that mediate tumorigenic transformation and metastasis. It also describes the cellular mechanisms that potentially explain the complex role of Rac in tumorigenesis. Finally, it discusses approaches for modulating Rac function as a potential anticancer strategy.
Sun
Di
D
Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Xu
Duo
D
Zhang
Baolin
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D020744:rac GTP-Binding Proteins / Q000502:physiology*
D000970:Antineoplastic Agents; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019255:NADPH Oxidases; D020744:rac GTP-Binding Proteins