Moores Cancer Center, University of California San Diego, La Jolla, California.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Clin Cancer Res. 2018 Feb 1;24(3):619-633. doi: 10.1158/1078-0432.CCR-17-1366. Epub 2017 Nov 16.
Recently, several comprehensive genomic analyses demonstrated and mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the pathway is closely related to HNSCC progression. However, the role of in HNSCC is less well understood. We analyzed pathway and downstream gene expression in the TCGA data set. To explore the functional role of , we performed proliferation, cisplatin viability, apoptosis, and cell-cycle assays. We also compared the relationships among , and epithelial-mesenchymal transition (EMT)-related genes using the TCGA data set and assays. is specifically upregulated in HNSCC compared with normal tissues in the TCGA data set. is more significantly related to activation in HNSCC in comparison with other receptors. promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell-cycle dysregulation. Furthermore, and upregulation resulted in decreased expression and increased , and expression. and expression was associated with an EMT phenotype as well as increased invasion and cell migration. In HNSCC, the pathway is specifically upregulated, induces proliferation and cisplatin resistance, and promotes EMT. .
最近，几项综合基因组分析表明，大约 20%的头颈部鳞状细胞癌（HNSCC）病例存在 和 突变。与其他类型的癌症类似，这些研究也表明， 通路与 HNSCC 的进展密切相关。然而， 在 HNSCC 中的作用还不太清楚。我们在 TCGA 数据集上分析了 通路和下游基因表达。为了探讨 的功能作用，我们进行了 增殖、顺铂活力、凋亡和细胞周期测定。我们还使用 TCGA 数据集和 测定比较了 之间以及上皮-间充质转化（EMT）相关基因之间的关系。与正常组织相比， 在 TCGA 数据集中特异性地上调。与其他 受体相比， 在 HNSCC 中与 激活的关系更为显著。 促进细胞增殖、顺铂耐药、抑制凋亡和细胞周期失调。此外， 和 的上调导致 的表达减少和 的增加，以及 的表达。 和 的表达与 EMT 表型相关，以及侵袭和细胞迁移增加。在 HNSCC 中， 通路特异性地上调，诱导增殖和顺铂耐药，并促进 EMT。
