TM4SF1 facilitates non-small cell lung cancer progression through regulating YAP-TEAD pathway
Objective: Transmembrane-4-L-Six-Family-1 (TM4SF1) has been implicated in tumor development and progression. This study aims to explore the impact of TM4SF1 on the proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) and uncover the underlying mechanisms.
Materials and Methods: TM4SF1 expression in human NSCLC tissues and cell lines was evaluated using qRT-PCR, immunohistochemistry, and Western blot analysis. Cell proliferation was assessed by CCK-8 and colony formation assays. Apoptosis was analyzed through flow cytometry, and cell migration and invasion were measured using wound healing and transwell assays. Co-immunoprecipitation (Co-IP) assays were performed to examine protein interactions, with Western blotting used to determine the expression levels of relevant proteins. In vivo experiments utilized xenograft tumor models.
Results: TM4SF1 expression was upregulated in NSCLC tissues and cell lines and was strongly associated with survival time, tumor size, lymph node metastasis, distant metastasis, and clinical stage. Both gain-of-function and loss-of-function experiments demonstrated that TM4SF1 promotes NSCLC cell proliferation, inhibits apoptosis, and enhances migration and invasion. Mechanistic studies revealed that TM4SF1 regulates the interaction between YAP and TEAD and modulates the expression of downstream target genes. Moreover, treatment with sh-YAP or Peptide 17 (a YAP-TEAD interaction inhibitor) reversed the effects of TM4SF1 on NSCLC cells. In vivo experiments further showed that TM4SF1 knockdown inhibited xenograft tumor growth in NSCLC.
Conclusions: This is the first study to show that TM4SF1 promotes proliferation, migration, and invasion in NSCLC, at least partially through the YAP-TEAD signaling pathway. These findings suggest that TM4SF1 could be a potential therapeutic target for NSCLC treatment.
IK-930