{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:18:49Z","timestamp":1792167529735,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Gerald Niznick College of Dentistry"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Oral cancer is a leading cause of cancer-related deaths and significantly affects the quality of life of patients. However, many of its mechanisms remain unclear, and its treatment needs improvement. The G-protein-coupled receptor taste receptor type 2 member 14 (T2R14 or TAS2R14) is expressed in various cancer types. However, few studies have investigated its roles in oral cancer, and its effects on oral cancer cell proliferation and growth are unknown. This study aimed to examine T2R14\u2019s impact on proliferation and cell population growth (CPG) of oral cancer cells. TAS2R14 gene knockout was performed, and cell numbers, cell viability, and colony formation were measured. This study showed that TAS2R14 knockout in oral cancer cells significantly decreased calcium mobilization, increased cell numbers, colony formation, the proliferation marker proliferating cell nuclear antigen, and the phosphorylation of mechanistic target of rapamycin, but did not affect cell viability. These observations are consistent with the clinical data that higher TAS2R14 mRNA expression is associated with better survival of patients with oral cancer. Therefore, T2R14 downregulation increased oral cancer CPG, suggesting a tumor-suppressor-like role. The study\u2019s findings could improve our understanding of T2R14 mechanisms and help develop strategies to advance oral cancer treatment by targeting T2R14.<\/jats:p>","DOI":"10.3390\/cells15030279","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:49:44Z","timestamp":1770036584000},"page":"279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of the G-Protein-Coupled Receptor T2R14 on Proliferation and Cell Population Growth in Oral Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-5674","authenticated-orcid":false,"given":"Yongqiang","family":"Chen","sequence":"first","affiliation":[{"name":"Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Dr. Gerald Niznick College of Dentistry, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3796-8122","authenticated-orcid":false,"given":"Manikanta","family":"Kella","sequence":"additional","affiliation":[{"name":"Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Dr. Gerald Niznick College of Dentistry, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Austin","sequence":"additional","affiliation":[{"name":"Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Dr. Gerald Niznick College of Dentistry, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajinder P.","family":"Bhullar","sequence":"additional","affiliation":[{"name":"Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Dr. Gerald Niznick College of Dentistry, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1129-7957","authenticated-orcid":false,"given":"Prashen","family":"Chelikani","sequence":"additional","affiliation":[{"name":"Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Dr. Gerald Niznick College of Dentistry, University of Manitoba, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Usman, S., Jamal, A., Teh, M.-T., and Waseem, A. (2021). Major Molecular Signaling Pathways in Oral Cancer Associated with Therapeutic Resistance. Front. Oral Health., 1.","DOI":"10.3389\/froh.2020.603160"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Menon, A., Mutalik, V.S., Chen, Y., Ponamgi, S., Peela, S., Schroth, R.J., Ghavami, S., and Chelikani, P. (2025). Beyond Genetics: Exploring Lifestyle, Microbiome, and Social Determinants in Oral Cancer Development. Cancers, 17.","DOI":"10.3390\/cancers17071094"},{"key":"ref_3","unstructured":"(2025, August 21). The Global Cancer Observatory. Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/cancers\/1-lip-oral-cavity-fact-sheet.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kumari, P., Debta, P., and Dixit, A. (2022). Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.825266"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1056\/NEJMsr2210097","article-title":"IARC Perspective on Oral Cancer Prevention","volume":"387","author":"Bouvard","year":"2022","journal-title":"New Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Molinero, J., Miguel\u00e1\u00f1ez-Medr\u00e1n, B.d.C., Puente-Guti\u00e9rrez, C., Delgado-Somolinos, E., Carreras-Presas, C.M., Fern\u00e1ndez-Farhall, J., and L\u00f3pez-S\u00e1nchez, A.F. (2021). Association between Oral Cancer and Diet: An Update. Nutrients, 13.","DOI":"10.3390\/nu13041299"},{"key":"ref_7","first-page":"e83242","article-title":"Oral Microbiome-Mediated Carcinogenesis in Oral Cavity Cancer: A Narrative Review","volume":"17","author":"Semiz","year":"2025","journal-title":"Cureus"},{"key":"ref_8","first-page":"1211","article-title":"Impact of human papillomavirus (HPV) infection on the development of oral squamous cell carcinoma (OSCC): A systematic review","volume":"62","author":"Kaczmarzyk","year":"2025","journal-title":"Dent. Med. Probl."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Navid, H.L., Akhavan, M., Jalali, P., Behrooz, A.B., Vakili, S., Vitorino, R., Beheshti, I., Menon, A., Mutalik, V.S., and Schroth, R.J. (2025). Hierarchical machine learning uncovers topological signatures of autophagy regulation by oral bacteria in oral squamous cell carcinoma. bioRxiv.","DOI":"10.64898\/2025.12.29.696881"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Das, S., Basak, S., and Sarkar, S. (2025). Decoding Salivary ncRNAomes as Novel Biomarkers for Oral Cancer Detection and Prognosis. Non-Coding RNA, 11.","DOI":"10.3390\/ncrna11020028"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kijowska, J., Grzegorczyk, J., Gliwa, K., J\u0119dras, A., and Sitarz, M. (2024). Epidemiology, Diagnostics, and Therapy of Oral Cancer\u2014Update Review. Cancers, 16.","DOI":"10.3390\/cancers16183156"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9991","DOI":"10.1038\/s41467-024-54157-6","article-title":"A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR","volume":"15","author":"Peri","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Singh, N., Ulmer, B., Medapati, M.R., Zhang, C., Schroth, R.J., Ghavami, S., and Chelikani, P. (2024). Bitter Taste Receptor T2R14 and Autophagy Flux in Gingival Epithelial Cells. Cells, 13.","DOI":"10.1101\/2024.01.17.576143"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113437","DOI":"10.1016\/j.celrep.2023.113437","article-title":"Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14","volume":"42","author":"Miller","year":"2023","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1500302","DOI":"10.1126\/sciadv.1500302","article-title":"Toxicology across scales: Cell population growth in vitro predicts reduced fish growth","volume":"1","author":"Schirmer","year":"2015","journal-title":"Sci. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41523-025-00787-y","article-title":"Exploring ID4 as a driver of aggression and a therapeutic target in triple-negative breast cancer","volume":"11","author":"Toro","year":"2025","journal-title":"npj Breast Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D1537","DOI":"10.1093\/nar\/gkaf952","article-title":"OncoDB 2.0: A comprehensive platform for integrated pan-cancer omics analysis","volume":"54","author":"Cho","year":"2026","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s42003-024-06326-y","article-title":"Pan-cancer discovery of somatic mutations from RNA sequencing data","volume":"7","author":"Tang","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D1334","DOI":"10.1093\/nar\/gkab970","article-title":"OncoDB: An interactive online database for analysis of gene expression and viral infection in cancer","volume":"50","author":"Tang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_20","first-page":"100625","article-title":"Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors","volume":"5","year":"2024","journal-title":"Innovation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1080\/15548627.2021.1973338","article-title":"Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth","volume":"18","author":"Chen","year":"2021","journal-title":"Autophagy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25054","DOI":"10.1074\/jbc.M114.576975","article-title":"Amino Acid Derivatives as Bitter Taste Receptor (T2R) Blockers","volume":"289","author":"Pydi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e21375","DOI":"10.1096\/fj.202000208R","article-title":"Bitter taste receptor T2R14 detects quorum sensing molecules from cariogenic Streptococcus mutans and mediates innate immune responses in gingival epithelial cells","volume":"35","author":"Medapati","year":"2021","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111286","DOI":"10.1016\/j.isci.2024.111286","article-title":"Bitter taste receptor T2R14-G\u03b1i coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis","volume":"27","author":"Singh","year":"2024","journal-title":"iScience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/nprot.2006.339","article-title":"Clonogenic assay of cells in vitro","volume":"1","author":"Franken","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.21037\/atm-21-6133","article-title":"The effects of proliferating cell nuclear antigen and p53 in patients with oral squamous cell carcinoma: A systematic review and meta-analysis","volume":"9","author":"Liu","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105943","DOI":"10.1016\/j.oraloncology.2022.105943","article-title":"PCNA and Ki67: Prognostic proliferation markers for oral cancer","volume":"130","author":"Jayaraman","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 signaling and the metabolic control of cell growth","volume":"45","author":"Manning","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","article-title":"Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease","volume":"8","author":"Panwar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s13402-025-01068-3","article-title":"Trends in immunotherapy for oral squamous cell carcinoma","volume":"48","author":"Xue","year":"2025","journal-title":"Cell. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/bs.acr.2019.11.002","article-title":"Targeting G protein-coupled receptors in cancer therapy","volume":"145","author":"Soond","year":"2020","journal-title":"Adv. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11010-019-03679-5","article-title":"Chemosensory bitter taste receptors T2R4 and T2R14 activation attenuates proliferation and migration of breast cancer cells","volume":"465","author":"Singh","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, L., Zhu, Q., Chen, S., Zhu, H., Li, C., Chen, J., and Li, X. (2025). Repurposing the bitter taste receptor TAS2R14 as a pro-ferroptotic driver in thyroid cancer via the STAT3-HCG11-miR-450b-5p axis. Acta Biochim. Biophys. Sin.","DOI":"10.3724\/abbs.2025198"},{"key":"ref_34","first-page":"ZC39","article-title":"Proliferating Cell Nuclear Antigen in Premalignancy and Oral Squamous Cell Carcinoma","volume":"9","author":"Poosarla","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100619","DOI":"10.1016\/j.oor.2024.100619","article-title":"Targeting the mTOR pathway: A new horizon in oral cancer treatment","volume":"11","author":"Devaraji","year":"2024","journal-title":"Oral Oncol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shafizadeh, M., Khan, M.W., Dr\u00f6gem\u00f6ller, B., Stavropoulou, C., John, P.S., Bhullar, R.P., Chelikani, P., and Hitchon, C.A. (2025). Genetic Variations in Bitter Taste Receptors and COVID-19 in the Canadian Longitudinal Study on Aging. Biomedicines, 13.","DOI":"10.3390\/biomedicines13102473"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Turner, G., Sywanycz, S.M., Buchler, B.L., Wardlow, R.D., Lee, R.J., and Carey, R.M. (2025). Quercetin as a Bitter Taste Receptor Agonist with Anticancer Effects in Head and Neck Cancer Cells. Nutrients, 17.","DOI":"10.1101\/2025.09.17.676947"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:54:55Z","timestamp":1770036895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cells15030279"],"URL":"https:\/\/doi.org\/10.3390\/cells15030279","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,1]]}}}