Abstract 234: Gαi2 induces cell migration in prostate cancer cells in the absence of rac1 activation

Abstract Prostate cancers can grow slowly and are confined to the prostate gland; However, metastatic prostate cancers are aggressive and can spread quickly. Gαi2 is a heterotrimeric G protein subunit and its essential for cell migration in prostate cancer cells, in response to both oxytocin and EGF, acting via GPCR and PTKR, respectively. The Rho family of GTPases includes RhoA, Rac1 and Cdc42, these are intracellular protein that regulate cell migration. In the previous studies we seen that the knockdown of Gαi2 reduces cell migration and lamellipodia formation at leading edge of PC3 cell overexpressing constitutively active Rac1, therefore Gαi2 may be involved in the regulation of cell motility and lamellipodia formation at a step which is independent or downstream of Rac1 activation. We hypothesize that Gαi2 is required for the activation of the downstream proteins of Rac1 leading to lamellipodia formation at the leading edge of migrating cells. We overexpressed constitutively active form of Gαi2 (Gαi2-Q205L) in PC3 parental cell lines. The result showed that when PC3 cells are transfected with Gαi2-Q205L the migration rate in these cells is significantly increased. In the parallel experiment we used a specific Gαi2 inhibitor, which resulted in attenuation of Giα2-Q205L effects on cell migration in PC3 cells. Furthermore, Rac1 inhibitor did not block increased cell migration in PC3 cells overexpressing constitutively active Gαi2. We studied Gαi2 effects on proteins activated by Rac1, specifically Wave2 and Arp 2/3. We transfected PC3 empty vector and PC3 Rac1 constitutively active stable cells with control siRNA or Gαi2 siRNA to knockdown endogenous Gαi2 expression. The western blot analysis showed Rac1 dependent activation of Wave2 and Arp 2/3 are impaired in the absence of Gαi2. We conclude activated Gαi2 plays a crucial role in cell migration in prostate cancer cells which is independent of Rac1 activation. Acknowledgement: These studies were supported by the NIH/NIMHD/RCMI under Award Number U54MD007590. Citation Format: Rarnice Johnson,Silvia Caggia,Shafiq Khan. Gαi2 induces cell migration in prostate cancer cells in the absence of rac1 activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 234.