Novel role of Gi?2 in cell migration: Downstream of PI3-kinase-AKT and Rac1 in prostate cancer cells
Caggie, Sylvia Chunduri, HimaBindu Millena, Ana C. Perkins, Jonathan N. Venugopal, Smrruthi V. Vo, BaoHan T. Ling, Chunliang Tu, Yaping Khan, Shafiq A.
2018-01
2010-2019
Tumor cell motility is the essential step in cancer metastasis. Previously, we showed that oxytocin and epidermal growth factor (EGF) effects on cell migration in prostate cancer cells require Gi?2 protein. In the current study, we investigated the interactions among G-protein coupled receptor (GPCR), Gi?2, PI3-kinase, and Rac1 activation in the induction of migratory and invasive behavior by diverse stimuli. Knockdown and knockout of endogenous Gi?2 in PC3 cells resulted in attenuation of transforming growth factor ?1 (TGF?1), oxytocin, SDF-1?, and EGF effects on cell migration and invasion. In addition, knockdown of Gi?2 in E006AA cells attenuated cell migration and overexpression of Gi?2 in LNCaP cells caused significant increase in basal and EGF-stimulated cell migration. Pretreatment of PC3 cells with Pertussis toxin resulted in attenuation of TGF?1- and oxytocin-induced migratory behavior and PI3-kinase activation without affecting EGF-induced PI3-kinase activation and cell migration. Basal- and EGF-induced activation of Rac1 in PC3 and DU145 cells were not affected in cells after Gi?2 knockdown. On the other hand, Gi?2 knockdown abolished the migratory capability of PC3 cells overexpressing constitutively active Rac1. The knockdown or knockout of Gi?2 resulted in impaired formation of lamellipodia at the leading edge of the migrating cells. We conclude that Gi?2 protein acts at two different levels which are both dependent and independent of GPCR signaling to induce cell migration and invasion in prostate cancer cells and its action is downstream of PI3-kinase-AKT-Rac1 axis.
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Clark Atlanta University Faculty Publications
Journal of Cellular Physiology
Clark Atlanta University
https://doi.org/10.1002/jcp.26894
http://hdl.handle.net/20.500.12322/cau.ir:2018_khan_shafiq_a
http://rightsstatements.org/vocab/InC/1.0/