{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:59:44Z","timestamp":1785945584529,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Georgia Research Alliance Venture","award":["U54MD007590"],"award-info":[{"award-number":["U54MD007590"]}]},{"name":"NIH\/NIMHD\/RCMI","award":["U54MD007590"],"award-info":[{"award-number":["U54MD007590"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metastatic prostate cancer occurs when the tumor spreads from the prostate gland to other parts of the body. Previous studies have shown that G\u03b1i2, a subunit of the heterotrimeric G protein complex, plays a critical role in inducing cell migration and invasion in prostate cancer cells in response to diverse stimuli. Rac1 is a small rho-GTPase, which is activated by the phosphoinositide 3-kinase (PI3K)\/AKT pathway and plays an essential role during cell migration. Previous studies have shown that the knockdown of G\u03b1i2 attenuates cell migration without causing any reduction in basal Rac1 activity in both PC3 and DU145 cells, and has only marginal effects on the epidermal growth facotor (EGF)-induced increase in Rac1 activity. Therefore, G\u03b1i2 may be involved in the regulation of cell motility and invasion independently or downstream of Rac1 activation. In this study, we investigated the possible mechanism of G\u03b1i2 at the level of the Rac1-dependent activation of Wiskott-Aldrich Syndrome Protein)-family verprolin homologous protein2 (Wave2) and actin related protein 2\/3 (Arp 2\/3) proteins, downstream effectors of activated Rac1. PC3 cells with a stable overexpression of constitutively active Rac1 were transfected with control siRNA or G\u03b1i2 siRNA to knockdown endogenous G\u03b1i2 expression. Western blot analysis showed that the Rac1-dependent activation of Wave2 was impaired in the absence of G\u03b1i2. The overexpression of constitutively active G\u03b1i2 (G\u03b1i2-Q205L) in PC3 cells significantly increased cell migration compared to cells transfected with control plasmids. In the parallel experiments, a specific G\u03b1i2 inhibitor blocked Gi\u03b12-Q205L-induced cell migration in PC3 cells. Furthermore, the Rac1 inhibitor did not block increased cell migration in PC3 cells overexpressing constitutively active G\u03b1i2. We conclude that activated G\u03b1i2 plays a crucial role in cell migration in prostate cancer cells independent of Rac1 activation.<\/jats:p>","DOI":"10.3390\/ijms26062663","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T06:36:23Z","timestamp":1742193383000},"page":"2663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["G\u03b1i2 Induces Cell Migration in PC3 Prostate Cancer Cells in the Absence of Rac1 Activation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7835-4900","authenticated-orcid":false,"given":"Rarnice","family":"Johnson","sequence":"first","affiliation":[{"name":"Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Dr, Atlanta, GA 30314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Caggia","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Dr, Atlanta, GA 30314, USA"},{"name":"Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Coral Gables, FL 33101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1010-313X","authenticated-orcid":false,"given":"Shafiq A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Dr, Atlanta, GA 30314, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3322\/caac.21235","article-title":"Cancer treatment and survivorship statistics, 2014","volume":"64","author":"DeSantis","year":"2014","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.urology.2012.04.007","article-title":"Treatment Patterns in Patients With Prostate Cancer and Bone Metastasis Among US Community-based Urology Group Practices","volume":"80","author":"Freedland","year":"2012","journal-title":"Urology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1615\/CritRevOncog.v18.i1-2.40","article-title":"On the origin of cancer metastasis","volume":"18","author":"Seyfried","year":"2013","journal-title":"Crit. Rev. 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