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

Publication ,  Journal Article
Rasheed, SAK; Leong, HS; Lakshmanan, M; Raju, A; Dadlani, D; Chong, F-T; Shannon, NB; Rajarethinam, R; Skanthakumar, T; Tan, EY; Hwang, JSG ...
Published in: Oncogene
March 2018

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.

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Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

March 2018

Volume

37

Issue

10

Start / End Page

1340 / 1353

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Squamous Cell Carcinoma of Head and Neck
  • Signal Transduction
  • Phenotype
  • Oncology & Carcinogenesis
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

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Rasheed, S. A. K., Leong, H. S., Lakshmanan, M., Raju, A., Dadlani, D., Chong, F.-T., … Iyer, N. G. (2018). GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers. Oncogene, 37(10), 1340–1353. https://doi.org/10.1038/s41388-017-0038-6
Rasheed, Suhail Ahmed Kabeer, Hui Sun Leong, Manikandan Lakshmanan, Anandhkumar Raju, Dhivya Dadlani, Fui-Teen Chong, Nicholas B. Shannon, et al. “GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.Oncogene 37, no. 10 (March 2018): 1340–53. https://doi.org/10.1038/s41388-017-0038-6.
Rasheed SAK, Leong HS, Lakshmanan M, Raju A, Dadlani D, Chong F-T, et al. GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers. Oncogene. 2018 Mar;37(10):1340–53.
Rasheed, Suhail Ahmed Kabeer, et al. “GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.Oncogene, vol. 37, no. 10, Mar. 2018, pp. 1340–53. Pubmed, doi:10.1038/s41388-017-0038-6.
Rasheed SAK, Leong HS, Lakshmanan M, Raju A, Dadlani D, Chong F-T, Shannon NB, Rajarethinam R, Skanthakumar T, Tan EY, Hwang JSG, Lim KH, Tan DS-W, Ceppi P, Wang M, Tergaonkar V, Casey PJ, Iyer NG. GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers. Oncogene. 2018 Mar;37(10):1340–1353.

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

March 2018

Volume

37

Issue

10

Start / End Page

1340 / 1353

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Squamous Cell Carcinoma of Head and Neck
  • Signal Transduction
  • Phenotype
  • Oncology & Carcinogenesis
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic