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The Rac GTPase in cancer: From old concepts to new paradigms

AutorKazanietz, Marcelo G.; Caloca, María J.
Fecha de publicación2017
EditorAmerican Association for Cancer Research
CitaciónCancer Research 77(20): 5445-5451 (2017)
ResumenRho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors, defects in Rac1 degradation, andmislocalization of Rac signaling components. The unexpected pro-oncogenic functions of Rac GTPase-activating proteins also challenged the dogma that these negative Rac regulators solely act as tumor suppressors. The potential contribution of Rac hyperactivation to resistance to anticancer agents, including targeted therapies, as well as to the suppression of antitumor immune response, highlights the critical need to develop therapeutic strategies to target the Rac pathway in a clinical setting.
URIhttp://hdl.handle.net/10261/158099
DOI10.1158/0008-5472.CAN-17-1456
Identificadoresdoi: 10.1158/0008-5472.CAN-17-1456
e-issn: 1538-7445
issn: 0008-5472
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