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Inhibiting G protein bg signaling blocks prostate cancer stem cell‐like properties and enhances the efficacy of paclitaxel
Author(s) -
Vaddi Prasanna K.,
Paudyal Prakash,
Xie Qing,
Chen Songhai
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1063.2
Subject(s) - du145 , prostate cancer , cancer research , cancer , cancer stem cell , metastasis , g protein coupled receptor , stem cell , cancer cell , prostate , paclitaxel , signal transduction , medicine , biology , microbiology and biotechnology , lncap
Aberrant activation of G protein‐coupled receptors (GPCRs) is implicated in prostate cancer progression. As a treatment strategy, however, targeting GPCR has been challenging because prostate cancer cells overexpress many GPCRs, which have redundant roles in cancer progression. To address this redundancy, we tried to block signaling via a hub through which multiple GPCRs converge — the G‐protein Gβγ subunits. Inhibiting signaling via Gβγ by overexpressing the scavernger, Gαt, or the Gβγ inhibitor, gallein, in several castration‐resistant prostate cancer cell lines (i.e. PC3, DU145 and 22Rv1), impaired cell growth and migration in vitro , and halted tumor growth and metastasis in nude mice. The blockade of Gβγ signaling also diminished prostate cancer stem cell‐like activities, by reducing tumorsphere formation in vitro and tumor formation in a limited dilution assay in nude mice. Furthermore, Gβγ blockade enhanced the sensitivity of prostate cancer cells to paclitaxel treatment, both in vitro and in vivo . Together, our results identify a novel function of Gβγ in regulating prostate cancer stem‐cell‐like activities, and demonstrate that targeting Gβγ signaling is an effective approach in blocking prostate cancer progression and augmenting response to chemotherapy. Support or Funding Information This work was supported in part by grants from NIH grant GM094255 (S. Chen) and DOD PCRP breakthrough award PC111628 (S. Chen).