Elevated TMEM45B expression promotes liver cancer progression and is associated with MET signaling activation.

Despite advancements in targeted therapies and immunotherapy, liver cancer (LC) remains a prominent contributor to cancer-related deaths globally, primarily attributable to its high recurrence and metastasis rates. Recent investigations have underscored the crucial function of transmembrane proteins in advancing cancer by regulating proliferation, invasion, and epithelial-mesenchymal transition (EMT). Transmembrane protein 45B (TMEM45B), a transmembrane protein implicated in tumor aggressiveness in various cancer types, requires further investigation to clarify its specific role in LC. This study investigates the expression patterns, biological functions, and underlying mechanisms of TMEM45B in LC. Bioinformatic analyses were conducted on publicly available datasets to evaluate TMEM45B expression in LC and its correlation with clinical outcomes. TMEM45B knockdown and overexpression models were established in LC cell lines through lentivirus-mediated shRNA and plasmid transfection. The CCK-8 assay evaluated the influence of TMEM45B on tumor cell proliferation. Cell migration and invasion were assessed by Transwell migration and Matrigel invasion assays, respectively. EMT-related changes were examined by immunofluorescence staining of vimentin and E-cadherin. MET signaling activity was assessed by Western Blotting. Tumor growth in vivo was evaluated using a subcutaneous xenograft model in nude mice. Elevated expression of TMEM45B was detected in LC cell lines and tissues, correlating with poor prognosis and advanced clinical stages. Cox regression analyses in a 66-patient cohort further indicated that TMEM45B was an independent prognostic factor for overall survival. Knockdown of TMEM45B in vitro significantly suppressed LC cell proliferation, invasion, migration, and EMT, while its overexpression exacerbated these malignant phenotypes. Mechanistically, TMEM45B promoted MET signaling activation, as reflected by increased MET protein levels and enhanced phosphorylation of downstream effectors AKT and ERK. Rescue experiments confirmed the crucial role of MET signaling in mediating TMEM45B-induced oncogenic effects. In vivo, TMEM45B knockdown notably hindered tumor growth and decreased EMT marker expression in a subcutaneous xenograft model. Our study suggests that TMEM45B may facilitate LC progression, at least in part, through MET signaling activation and EMT induction. These results underscore TMEM45B's significance as a prognostic indicator and therapeutic target in LC. Further research on developing TMEM45B-targeted therapy could improve the effectiveness of treating advanced LC patients.