Abstract
Three GTPases, RAC, RHO, and Cdc42, play essential roles in coordinating many cellular functions during embryonic development, both in healthy cells and in disease conditions like cancers. We have presented patterns of distribution of the frequency of RAC1-alteration(s) in cancers as obtained from cBioPortal. With this background data, we have interrogated the various functions of RAC1 in tumors, including proliferation, metastasis-associated phenotypes, and drug-resistance with a special emphasis on solid tumors in adults. We have reviewed the activation and regulation of RAC1 functions on the basis of its sub-cellular localization in tumor cells. Our review focuses on the role of RAC1 in cancers and summarizes the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of RAC1-PAK targeting agents.
Highlights
Translational Oncology Laboratory, Avera Cancer Institute, Sioux Falls, SD 57105, USA; Departmental of Internal Medicine, SSOM, University of South Dakota, Sioux Falls, SD 57105, USA
More than half of the cancer types is the characteristic feature of alterations of the RAC1 gene in Bladder/urinary tract cancers, lung cancers, and melanoma are the cancers among which a higher cancers
RAC1 GTPases, small G-proteins widely implicated in tumorigenesis and metastasis, transduce signals from receptor tyrosine-kinases (e.g., EGFR/ HER2) or non-receptor tyrosine kinases (e.g., SRC, FAK), G-protein-coupled receptors (GPCRs), and integrins and control a number of essential cellular functions, including motility, adhesion, and proliferation
Summary
Over 80 GEFs (guanine nucleotide exchange factors) and more than 70 GAPs (GTPase-activating proteins) have been reported, suggesting that Rho-family GTPase regulation is complex and that activity and localization can be modulated by a multitude of signaling pathways depending on the spatiotemporal context [3]. RAC1, but not RAC2 or RAC3 genes, contains an additional exon 3b that is included by alternative splicing in the variant of RAC1b, a constitutively active mutant that is expressed primarily in colon and breast cancer [6]. Cells 2019, 8, x expression/activity of RAC guanine nucleotide exchange factors responsible forresponsible. RAC activation has Deregulated expression/activity of RAC guanine nucleotide exchange factors for RAC been largely associated with a metastatic phenotype and drug resistance. Activation has been largely associated with a metastatic phenotype and drug resistance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
