T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma.
T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma.
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DOI：
10.1002/1878-0261.13131
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发表时间：
2022-04
影响因子：
6.6
通讯作者：
Lee RJ
中科院分区：
文献类型：
--
作者：
Carey RM;McMahon DB;Miller ZA;Kim T;Rajasekaran K;Gopallawa I;Newman JG;Basu D;Nead KT;White EA;Lee RJ
更好地管理头颈鳞状细胞癌 (HNSCC) 需要更清楚地了解肿瘤生物学和疾病风险。苦味受体（T2R）已在多种癌症中进行了研究，包括甲状腺癌、唾液癌和胃肠道癌，但其在 HNSCC 中的作用尚未被探索。我们发现 HNSCC 患者样本和细胞系在细胞膜和核膜上均表达功能性 T2R。苦味化合物，包括细菌代谢物，激活 T2R 介导的核 Ca2+ 反应，导致线粒体去极化、半胱天冬酶激活，并最终导致细胞凋亡。缓冲核 Ca2+ 升高可阻断 caspase 激活。此外，癌症基因组图谱中 HNSCC 中 T2R 表达的增加与总体生存率的提高相关。这项工作表明，T2R 是预测结果和指导治疗选择的潜在生物标志物，可用作刺激肿瘤细胞凋亡的治疗靶标，并可介导 HNSCC 中的肿瘤微生物组串扰。头颈鳞状细胞癌 (HNSCC) 细胞在细胞膜和核膜上表达苦味受体 (T2R)。 T2R 被各种苦味化合物（包括分泌的细菌产物）激活，导致核钙 (Ca2+) 反应、半胱天冬酶激活、线粒体去极化和细胞凋亡。表达较高水平 T2R 的 HNSCC 肿瘤与改善的总体生存率相关。使用 BioRender 创建。
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 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. Head and neck squamous cell carcinoma (HNSCC) cells express bitter taste receptors (T2Rs) on the cell and nuclear membranes. T2Rs are activated by various bitter compounds including secreted bacterial products, leading to nuclear calcium (Ca2+) responses, caspase activation, mitochondrial depolarization, and apoptosis. HNSCC tumors that express higher levels of T2Rs are associated with improved overall survival. Created with BioRender.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
9.8
作者：
Albeck JG;Burke JM;Spencer SL;Lauffenburger DA;Sorger PK
通讯作者：
Sorger PK
影响因子：
4.6
作者：
Banerjee S;Tian T;Wei Z;Peck KN;Shih N;Chalian AA;O'Malley BW;Weinstein GS;Feldman MD;Alwine J;Robertson ES
通讯作者：
Robertson ES
DOI：
10.1186/s41199-016-0016-7
发表时间：
2016-01-01
期刊：
Cancers of the head & neck
影响因子：
--
作者：
An, Yi;Holsinger, F Christopher;Husain, Zain A
通讯作者：
Husain, Zain A
影响因子：
8
作者：
Gopallawa, Indiwari;Freund, Jenna R.;Lee, Robert J.
通讯作者：
Lee, Robert J.