Department of Otolaryngology, University of Minnesota, Minneapolis, MN, U.S.A.
Anticancer Res. 2020 Oct;40(10):5417-5421. doi: 10.21873/anticanres.14551.
Type II diabetes agents have anticancer effects on head and neck squamous cell carcinoma (HNSCC). The mechanistic target of rapamycin (MTOR) pathway represents a putative target.
We interrogated an Affymetrix HNSCC dataset for MTOR-related gene expression.
MTOR expression itself was unchanged, but various related genes demonstrated differential expression. Pathway promoters ras homolog (RHEB), MTOR-associated protein (MLST8), and ribosomal protein S6 kinase B1 (RPS6KB1) were up-regulated. Expression of growth suppressors tuberous sclerosis complex 2 (TSC2), programmed cell death 4 (PDCD4), and BCL2 apoptosis regulator-associated agonist of cell death (BAD) were reduced in HNSCC. Upstream, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), AKT serine/threonine kinase 1 (AKT1), and phosphatase and tensin homolog (PTEN) were up-regulated in cancer.
Several MTOR pathway promoters and tumor suppressors were found to be differentially expressed, favoring MTOR pathway up-regulation in HNSCC. Genomic databases can be interrogated to identify intervention targets and endpoints in HNSCC trials.
II 型糖尿病药物对头颈部鳞状细胞癌（HNSCC）具有抗癌作用。雷帕霉素（MTOR）途径的机制靶点代表了一个潜在的靶点。
我们在 Affymetrix HNSCC 数据集上对 MTOR 相关基因表达进行了研究。
MTOR 表达本身没有改变，但各种相关基因表现出差异表达。途径启动子 ras 同源物（RHEB）、MTOR 相关蛋白（MLST8）和核糖体蛋白 S6 激酶 B1（RPS6KB1）上调。肿瘤抑制因子结节性硬化复合物 2（TSC2）、程序性细胞死亡 4（PDCD4）和 BCL2 凋亡调节因子相关的细胞死亡促进剂（BAD）在 HNSCC 中的表达降低。在上游，磷酸肌醇-4,5-二磷酸 3-激酶催化亚单位 α（PIK3CA）、AKT 丝氨酸/苏氨酸激酶 1（AKT1）和磷酸酶和张力蛋白同源物（PTEN）在癌症中上调。
发现几种 MTOR 途径启动子和肿瘤抑制因子表达差异，有利于 HNSCC 中 MTOR 途径的上调。可以对基因组数据库进行查询，以确定 HNSCC 试验中的干预靶点和终点。
