Abstract
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 Giα2 protein. In the current study, we investigated the interactions among G-protein coupled receptor (GPCR), Giα2, PI3-kinase, and Rac1 activation in the induction of migratory and invasive behavior by diverse stimuli. Knockdown and knockout of endogenous Giα2 in PC3 cells resulted in attenuation of transforming growth factor β1 (TGFβ1), oxytocin, SDF-1α, and EGF effects on cell migration and invasion. In addition, knockdown of Giα2 in E006AA cells attenuated cell migration and overexpression of Giα2 in LNCaP cells caused significant increase in basal and EGF-stimulated cell migration. Pretreatment of PC3 cells with Pertussis toxin resulted in attenuation of TGFβ1- 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 Giα2 knockdown. On the other hand, Giα2 knockdown abolished the migratory capability of PC3 cells overexpressing constitutively active Rac1. The knockdown or knockout of Giα2 resulted in impaired formation of lamellipodia at the leading edge of the migrating cells. We conclude that Giα2 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 802-815 |
| Number of pages | 14 |
| Journal | Journal of Cellular Physiology |
| Volume | 234 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2018 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
Novel role of Giα2 in cell migration : Downstream of PI3-kinase–AKT and Rac1 in prostate cancer cells. / Caggia, Silvia; Chunduri, Hima Bindu; Millena, Ana C.; Perkins, Jonathan N.; Venugopal, Smrruthi V.; Vo, Bao Han T.; Li, Chunliang; Tu, Yaping; Khan, Shafiq A.
In: Journal of Cellular Physiology, Vol. 234, No. 1, 01.01.2018, p. 802-815.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel role of Giα2 in cell migration
T2 - Downstream of PI3-kinase–AKT and Rac1 in prostate cancer cells
AU - Caggia, Silvia
AU - Chunduri, Hima Bindu
AU - Millena, Ana C.
AU - Perkins, Jonathan N.
AU - Venugopal, Smrruthi V.
AU - Vo, Bao Han T.
AU - Li, Chunliang
AU - Tu, Yaping
AU - Khan, Shafiq A.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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 Giα2 protein. In the current study, we investigated the interactions among G-protein coupled receptor (GPCR), Giα2, PI3-kinase, and Rac1 activation in the induction of migratory and invasive behavior by diverse stimuli. Knockdown and knockout of endogenous Giα2 in PC3 cells resulted in attenuation of transforming growth factor β1 (TGFβ1), oxytocin, SDF-1α, and EGF effects on cell migration and invasion. In addition, knockdown of Giα2 in E006AA cells attenuated cell migration and overexpression of Giα2 in LNCaP cells caused significant increase in basal and EGF-stimulated cell migration. Pretreatment of PC3 cells with Pertussis toxin resulted in attenuation of TGFβ1- 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 Giα2 knockdown. On the other hand, Giα2 knockdown abolished the migratory capability of PC3 cells overexpressing constitutively active Rac1. The knockdown or knockout of Giα2 resulted in impaired formation of lamellipodia at the leading edge of the migrating cells. We conclude that Giα2 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.
AB - 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 Giα2 protein. In the current study, we investigated the interactions among G-protein coupled receptor (GPCR), Giα2, PI3-kinase, and Rac1 activation in the induction of migratory and invasive behavior by diverse stimuli. Knockdown and knockout of endogenous Giα2 in PC3 cells resulted in attenuation of transforming growth factor β1 (TGFβ1), oxytocin, SDF-1α, and EGF effects on cell migration and invasion. In addition, knockdown of Giα2 in E006AA cells attenuated cell migration and overexpression of Giα2 in LNCaP cells caused significant increase in basal and EGF-stimulated cell migration. Pretreatment of PC3 cells with Pertussis toxin resulted in attenuation of TGFβ1- 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 Giα2 knockdown. On the other hand, Giα2 knockdown abolished the migratory capability of PC3 cells overexpressing constitutively active Rac1. The knockdown or knockout of Giα2 resulted in impaired formation of lamellipodia at the leading edge of the migrating cells. We conclude that Giα2 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.
UR - http://www.scopus.com/inward/record.url?scp=85052441787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052441787&partnerID=8YFLogxK
U2 - 10.1002/jcp.26894
DO - 10.1002/jcp.26894
M3 - Article
C2 - 30078221
AN - SCOPUS:85052441787
VL - 234
SP - 802
EP - 815
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 1
ER -