CTTN overexpression in HNSCC inhibits Anoikis-apoptosis

作者：Zheng-Zhong Shen, Qiu-Shuang Xu, Chuanfang Wu, Xiaodong Feng, Qianming Chen · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-21891-w · 被引用次数：7 · 研究领域：Cell Adhesion Molecules Research、Cell death mechanisms and regulation、Wnt/β-catenin signaling in development and cancer

Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent and heterogeneous malignancy. Normal cells maintain their homeostasis through Anoikis, and tumor cells enhance their own invasion and migration by resisting Anoikis. The search for biomarkers of resistance to Anoikis in head and neck tumors could be helpful in evaluating the prognosis of patients as well as in finding therapeutic targets for HNSCC due to the lack of more definitive biomarkers in HNSCC. HNSCC cells were cultured in suspension, and HNSCC cells were found to undergo apoptosis after losing the support of ECM.LASSO-Cox regression analysis was applied to the TCGA-HNSC cohort to evaluate the prognostic value of apoptosis-associated genes, resulting in the construction of an apoptosis-related prognostic model (CTTN, PLAU, PLK1, BID, MAPK11, SPINK1, VEGFA, PIK3R2, CEACAM1, MAD2L1, SLCO1B3, TFDP1, SFRP1, SPP1, SPHK1). A risk score-based nomogram was developed to optimally predict survival in HNSCC patients. The role of the prognostic model gene CTTN in HNSCC apoptosis was validated via PI staining, IF, and WB. Knockdown of CTTN affected FAK expression levels in cells, reducing their anti-apoptotic capacity by impairing cytoskeletal formation. We validated CTTN function in HNSCC-PDOs. We analyzed the role of CTTN and its major subpopulations in pan-cancer and HNSCC. Silencing CTTN significantly suppressed growth in patient-derived organoids (PDOs) from HNSCC patients. CTTN was highly expressed in most t...