GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers

Oncogene. 2018 Mar;37(10):1340-1353. doi: 10.1038/s41388-017-0038-6. Epub 2017 Dec 19.


Treatment failure in solid tumors occurs due to the survival of specific subpopulations of cells that possess tumor-initiating (TIC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) in cancer progression and the acquisition of TIC phenotypes. Many of the implicated GPCRs signal through the G protein GNA13. In this study, we demonstrate that GNA13 is upregulated in many solid tumors and impacts survival and metastases in patients. GNA13 levels modulate drug resistance and TIC-like phenotypes in patient-derived head and neck squamous cell carcinoma (HNSCC) cells in vitro and in vivo. Blockade of GNA13 expression, or of select downstream pathways, using small-molecule inhibitors abrogates GNA13-induced TIC phenotypes, rendering cells vulnerable to standard-of-care cytotoxic therapies. Taken together, these data indicate that GNA13 expression is a potential prognostic biomarker for tumor progression, and that interfering with GNA13-induced signaling provides a novel strategy to block TICs and drug resistance in HNSCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • GTP-Binding Protein alpha Subunits / genetics*
  • GTP-Binding Protein alpha Subunits, G12-G13 / genetics
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Phenotype
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GNA13 protein, human
  • GTP-Binding Protein alpha Subunits
  • GTP-Binding Protein alpha Subunits, G12-G13