HSF1 activates the FOXO3a–ΔNp63α–CDK4 axis to promote head and neck squamous cell carcinoma cell proliferation and tumour growth. Issue 8 (7th February 2023)

• Record Type: Journal Article
• Authors: Wang, Yuemeng; Zhu, Qile; Guo, Shiya; Ao, Juan; Zhang, Wenhua; Fei, Junjie; Yu, Shuhan; Niu, Mengmeng; Zhang, Yujun; Sherman, Michael Y.; Xiao, Zhi‐Xiong Jim; Yi, Yong
• Is Part Of: FEBS letters. Volume 597:Issue 8(2023)
• Page Start: 1125
• Page End: 1137
• Publication Date: 2023-02-07
• Subjects: FOXO3a -- HNSCC -- HSF1 -- tumour growth -- ΔNp63α; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14588
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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 expression and HNSCC tumour growth. Ablation of HSF1 or treatment with KRIBB11, a specific pharmacological inhibitor of HSF1, significantly suppresses ΔNp63α expression and HNSCC tumour growth. Clinically, the expression of HSF1 is positively correlated with the expression of ΔNp63α in HNSCC tumours. Together, this study demonstrates that the HSF1–ΔNp63α pathway is critically important for HNSCC tumour growth. Abstract : Heat shock factor 1 (HSF1) is essential for head and neck squamous cell carcinoma (HNSCC) growth. HSF1 promotes forkhead box protein O3a ‐mediated transcription of ΔNp63α, which in turn promotes CDK4 expression and facilitates HNSCC cell proliferation and tumour growth. Pharmacological inhibition of HSF1 significantly suppresses HNSCC tumour growth, highlighting that HSF1 may be a promising therapeutic target for HNSCC treatment.