高铁F1
头颈部鳞状细胞癌
癌症研究
细胞生长
转录因子
生物
细胞周期
热冲击系数
下调和上调
热休克蛋白
细胞
癌症
细胞生物学
头颈部癌
遗传学
热休克蛋白70
基因
作者
Yuemeng Wang,Qile Zhu,Shiya Guo,Juan Ao,Wenhua Zhang,Junjie Fei,Shuhan Yu,Mengmeng Niu,Yujun Zhang,Michael Y Sherman,Zhi-Xiong Jim Xiao,Yong Yi
标识
DOI:10.1002/1873-3468.14588
摘要
Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. Heat shock factor 1 (HSF1) is a conserved transcriptional factor that plays a critical role in maintaining cellular proteostasis. However, the role of HSF1 in HNSCC development remains largely unclear. Here, we report that HSF1 promotes forkhead box protein O3a (FOXO3a)-dependent transcription of ΔNp63α (p63 isoform in the p53 family; inhibits cell migration, invasion, and metastasis), which leads to upregulation of cyclin-dependent kinase 4 (CDK4) expression and HNSCC tumor growth. Ablation of HSF1 or treatment with KRIBB11, a specific pharmacological inhibitor of HSF1, significantly suppresses ΔNp63α expression and HNSCC tumor growth. Clinically, the expression of HSF1 is positively correlated with the expression of ΔNp63α in HNSCC tumors. Together, this study demonstrates that the HSF1-ΔNp63α pathway is critically important for HNSCC tumor growth.
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