RESUMO
Family with sequence similarity 135 member B (FAM135B) is a novel cancer-implicated gene in esophageal squamous cell carcinoma (ESCC). However, little is known regarding its biological functions and mechanisms in ESCC. Here, we identified FAM135B high expression was associated with lymph node metastasis and infiltrating development of ESCC. Elevated FAM135B expression promoted ESCC migration and invasion in vitro and lung metastasis in vivo. Furthermore, epithelial mesenchymal transition (EMT)-related pathways were enriched with differentially expressed genes (DEGs) in high FAM135B ESCC samples and FAM135B positively regulated EMT markers. Mechanistically, we observed FAM135B interacted with the intermediate domain of TRAF2 and NCK-interacting kinase (TNIK), activating the Wnt/ß-catenin signaling pathway. The facilitation of TNIK on ESCC migration and invasion was reversed by FAM135B siRNA. Additionally, N6-Methyladenosine (m6A) modification stabilized FAM135B mRNA and positively regulated FAM135B expression, with Methyltransferase like 3 (METTL3) as its substantial m6A writer. The pro-EMT effects of METTL3 overexpression were rescued by silencing FAM135B. Collectively, METTL3-mediated upexpression of FAM135B activated TNIK-dependent Wnt/ß-catenin pathway, highlighting the pivotal role of FAM135B driver in ESCC progression.
