上海交通大学学报（医学版）2025，Vol.45Issue(4)：404-414,11.DOI:10.3969/j.issn.1674-8115.2025.04.002
Fas相关死亡结构域蛋白促进头颈部鳞状细胞癌细胞增殖能力的机制研究
Mechanism of Fas-associated protein with death domain in promoting proliferation of head and neck squamous cell carcinoma cells
摘要
Abstract
Objective·To detect the expression level of Fas-associated protein with death domain(FADD)in head and neck squamous cell carcinoma(HNSCC)and to explore the molecular mechanisms by which FADD promotes the proliferation of HNSCC cells.Methods·The GEPIA 2 database was utilized to analyze the expression level of FADD in tumor tissues and to evaluate its association with prognosis.Immunohistochemistry staining(IHC)was performed on HNSCC tissues to investigate the changes in FADD expression levels in normal,dysplastic,and tumor tissues.Stable FADD-knockdown Fadu and HSC3 cell lines were constructed and validated using Western blotting and quantitative real-time PCR(qRT-PCR).The regulatory effect of FADD on the proliferation of HNSCC cells was explored using the LiveCyte live-cell tracking system,colony formation assay,and cell viability assay.Proteins interacting with FADD were identified by co-immunoprecipitation mass spectrometry(Co-IP/MS),and further mechanistic studies were conducted using CRISPR/Cas9 technology,LiveCyte live-cell tracking system,and Western blotting.Results·Analysis of the GEPIA2 database indicated that FADD was significantly overexpressed in head and neck cancer and was associated with poor prognosis.IHC staining showed that FADD expression levels progressively increased from normal to dysplastic to tumor tissues in HNSCC patients.Knockdown of FADD in HNSCC cells resulted in significantly reduced proliferation and colony formation compared to the control group.Co-IP/MS results showed that FADD interacted with the CUX1 protein,and FADD knockdown led to increased CUX1 expression.Moreover,CUX1 knockdown significantly promoted HNSCC cell proliferation and reversed the anti-proliferative phenotype caused by FADD knockdown.Conclusion·FADD plays a significant pro-carcinogenic role in HNSCC and is associated with poor prognosis.FADD can further regulate tumor cell proliferation by interacting with CUX1 and suppressing its expression level.关键词
Fas相关死亡结构域蛋白/CUT样同源盒 1/头颈部鳞状细胞癌/细胞增殖Key words
Fas-associated protein with death domain(FADD)/CUT-like homeobox 1(CUX1)/head and neck squamous cell carcinoma(HNSCC)/cell proliferation分类
医药卫生引用本文复制引用
陈怡楠,郑旸,曾汉林,雷鸣..Fas相关死亡结构域蛋白促进头颈部鳞状细胞癌细胞增殖能力的机制研究[J].上海交通大学学报（医学版）,2025,45(4):404-414,11.基金项目
国家自然科学基金青年项目(82204421). The National Natural Science Foundation of China(82204421). （82204421）
