J Cancer
2018; 9(4):711-725.
doi:10.7150/jca.21803 This issueCite
Research Paper
Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10
Louisa Stern1, Nathalia Giese1, Thilo Hackert1, Oliver Strobel1, Peter Schirmacher2, Klaus Felix1, Matthias M. Gaida2✉
1. Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany 2. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
✉ Corresponding author: Matthias M. Gaida, M.D., Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, D-69120 Heidelberg, Germany. Tel: +49-6221 56-4161; Fax: +49 6221 56 -5251; email: Matthias.Gaidauni-heidelberg.de
Citation:
Stern L, Giese N, Hackert T, Strobel O, Schirmacher P, Felix K, Gaida MM. Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10. J Cancer 2018; 9(4):711-725. doi:10.7150/jca.21803. https://www.jcancer.org/v09p0711.htm
Bitter taste receptors (T2Rs) are G-protein coupled transmembrane proteins initially identified in the gustatory system as sensors for the taste of bitter. Recent evidence on expression of these receptors outside gustatory tissues suggested alternative functions, and there is growing interest of their potential role in cancer biology. In this study, we report for the first time, expression and functionality of the bitter receptor family member T2R10 in both human pancreatic ductal adenocarcinoma (PDAC) tissue and PDAC derived cell lines. Caffeine, a known ligand for T2R10, rendered the tumor cells more susceptible to two standard chemotherapeutics, Gemcitabine and 5-Fluoruracil. Knocking down T2R10 in the cell line BxPC-3 reduced the caffeine-induced effect. As possible underlying mechanism, we found that caffeine via triggering T2R10 inhibited Akt phosphorylation and subsequently downregulated expression of ABCG2, the so-called multi-drug resistance protein that participates in rendering cells resistant to a variety of chemotherapeutics. In conclusion, T2R10 is expressed in pancreatic cancer and it downmodulates the chemoresistance of the tumor cells.
Stern, L., Giese, N., Hackert, T., Strobel, O., Schirmacher, P., Felix, K., Gaida, M.M. (2018). Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10. Journal of Cancer, 9(4), 711-725. https://doi.org/10.7150/jca.21803.
ACS
Stern, L.; Giese, N.; Hackert, T.; Strobel, O.; Schirmacher, P.; Felix, K.; Gaida, M.M. Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10. J. Cancer 2018, 9 (4), 711-725. DOI: 10.7150/jca.21803.
NLM
Stern L, Giese N, Hackert T, Strobel O, Schirmacher P, Felix K, Gaida MM. Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10. J Cancer 2018; 9(4):711-725. doi:10.7150/jca.21803. https://www.jcancer.org/v09p0711.htm
CSE
Stern L, Giese N, Hackert T, Strobel O, Schirmacher P, Felix K, Gaida MM. 2018. Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10. J Cancer. 9(4):711-725.
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