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The G protein Gαs acts as a tumor suppressor in sonic hedgehog signaling-driven tumorigenesis

Rohit Rao1, Ralph Salloum2, Mei Xin2

  • 1a University of Cincinnati Medical Scientist Training Program , Cincinnati , OH , USA.

Cell Cycle (Georgetown, Tex.)
|April 8, 2016
PubMed

Insights

Loss of G protein-coupled receptor Gαs signaling promotes tumor growth by activating Sonic Hedgehog and Hippo pathways. Targeting this pathway may offer novel cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • G protein-coupled receptors (GPCRs) play complex roles in tumor development.
  • Redundant GPCR signaling complicates targeted cancer therapies.
  • Gαs signaling, downstream of GPCRs, exhibits context-dependent roles in tumorigenesis.

Purpose of the Study:

  • To review the novel tumor-suppressive functions of Gαs signaling in ectodermal-derived neoplasms.
  • To elucidate the mechanisms by which Gαs inhibits Sonic Hedgehog (SHH) and Hippo pathways.
  • To explore therapeutic strategies targeting the Gαs pathway for cancer treatment.

Main Methods:

  • Review of existing literature on GPCRs, Gαs signaling, SHH, and Hippo pathways in cancer.
  • Analysis of GNAS gene function and its impact on progenitor cell proliferation.
  • Examination of Gαs-mediated regulation of cAMP-PKA and NF2-LATS1/2-Yap signaling.

Main Results:

  • Gαs acts as a tumor suppressor in neural and epidermal stem/progenitor cells.
  • Loss of GNAS leads to SHH and Hippo pathway activation, promoting progenitor cell over-proliferation and tumor formation.
  • Gαs signaling inhibits self-renewal by suppressing SHH and Hippo pathways via cAMP-PKA activation.

Conclusions:

  • The Gαs-regulated signaling network is crucial for suppressing SHH-driven tumorigenesis.
  • Targeting Gαs-mediated pathways presents a promising therapeutic avenue for inhibiting tumor growth and progression.
  • Understanding Gαs's dual role in cancer is key to developing effective treatments.
Keywords:
Basal cell carcinomaG-proteinGNASGPCRsGαsHedgehog signalingHippo signalingStem cellscAMP-dependent PKAmedulloblastoma

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