RT Journal Article
SR Electronic
T1 T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.17.444527
DO 10.1101/2021.05.17.444527
A1 Ryan M. Carey
A1 Derek B. McMahon
A1 Karthik Rajasekaran
A1 Indiwari Gopallawa
A1 Jason G. Newman
A1 Devraj Basu
A1 Elizabeth A. White
A1 Robert J. Lee
YR 2021
UL http://biorxiv.org/content/early/2021/05/17/2021.05.17.444527.abstract
AB Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes. Bitter compounds, including bacterial metabolites, activated T2R-mediated nuclear Ca2+ responses leading to mitochondrial depolarization, caspase activation and ultimately apoptosis. Buffering nuclear Ca2+ elevation blocked caspase activation. Furthermore, increased expression of T2Rs in HNSCCs from The Cancer Genome Atlas (TCGA) is associated with improved overall survival. This work suggests that T2Rs are potential biomarkers to predict outcomes and guide treatment selection, may be leveraged as therapeutic targets to stimulate tumor apoptosis, and may mediate tumor-microbiome crosstalk in HNSCC.Competing Interest StatementThe authors have declared no competing interest.