Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41388-017-0038-6
Title: GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers
Authors: Rasheed, S.A.K 
Leong, H.S
Lakshmanan, M
Raju, A
Dadlani, D 
Chong, F.-T
Shannon, N.B
Rajarethinam, R
Skanthakumar, T
Tan, E.Y
Hwang, J.S.G 
Lim, K.H 
Tan, D.S.-W 
Ceppi, P
Wang, M 
Tergaonkar, V 
Casey, P.J 
Iyer, N.G 
Keywords: antineoplastic agent
cisplatin
cytotoxic agent
GNA13 protein
GNA13 protein inhibitor
guanine nucleotide binding protein
protein inhibitor
tumor marker
unclassified drug
antineoplastic agent
guanine nucleotide binding protein alpha subunit
tumor marker
animal cell
animal experiment
animal model
animal tissue
Article
cancer growth
cancer patient
cancer prognosis
cancer resistance
cancer survival
carcinoma cell
controlled study
head and neck squamous cell carcinoma
human
human cell
in vitro study
in vivo study
metastasis
mouse
nonhuman
phenotype
priority journal
protein expression
protein function
randomized controlled trial
signal transduction
solid malignant neoplasm
tumor initiating phenotype
upregulation
animal
cell proliferation
cell transformation
drug effect
drug resistance
drug therapy
gene expression regulation
genetics
nonobese diabetic mouse
pathology
phenotype
SCID mouse
tumor cell culture
Animals
Antineoplastic Agents
Biomarkers, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
GTP-Binding Protein alpha Subunits
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Phenotype
Signal Transduction
Squamous Cell Carcinoma of Head and Neck
Tumor Cells, Cultured
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Rasheed, S.A.K, Leong, H.S, Lakshmanan, M, Raju, A, Dadlani, D, Chong, F.-T, Shannon, N.B, Rajarethinam, R, Skanthakumar, T, Tan, E.Y, Hwang, J.S.G, Lim, K.H, Tan, D.S.-W, Ceppi, P, Wang, M, Tergaonkar, V, Casey, P.J, Iyer, N.G (2018). GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers. Oncogene 37 (10) : 1340-1353. ScholarBank@NUS Repository. https://doi.org/10.1038/s41388-017-0038-6
Abstract: 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. © 2017 The Author(s).
Source Title: Oncogene
URI: https://scholarbank.nus.edu.sg/handle/10635/175123
ISSN: 0950-9232
DOI: 10.1038/s41388-017-0038-6
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