FAM96A suppresses epithelial-mesenchymal transition and tumor metastasis by inhibiting TGFβ1 signals.

Metastasis is the main cause of death in 90% of patients with tumors, and epithelial-mesenchymal transition (EMT) plays a key role in this process. Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved protein related to cytosolic iron assembly. However, no research has been conducted on its role in tumor metastasis. Bioinformatics analysis with Kaplan-Meier analysis showed that patients with lower FAM96A expression in different tumors had shorter survival times and poorer prognoses. Here, we identified FAM96A as a crucial regulator of the TGFβ signaling pathway because it inhibits TGFβ-mediated tumor metastasis and EMT. FAM96A did not affect the proliferation or apoptosis of tumor cells but significantly reduced their migration and invasion abilities in vitro. The colonization and metastatic abilities of FAM96A-knockout tumor cells were significantly enhanced in vivo. Furthermore, the overexpression of exogenous FAM96A inhibited TGFβ-induced EMT through the SMAD-mediated pathway and downregulated the expression of endogenous transforming growth factor-β1 (TGFβ1). These findings demonstrated a correlation between EMT and FAM96A gene expression for the first time, which is highly important for revealing the mechanism underlying tumor metastasis.