"TFEB-HNRNPA2B1": A positive feedback loop facilitating metastasis in hepatocellular carcinoma cells

This study elucidated the regulatory role of the TFEB-HNRNPA2B1 feedback loop in hepatocellular carcinoma (HCC) metastasis, a highly prevalent and aggressive liver cancer subtype. The findings demonstrated that transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, was significantly upregulated in HCC tissues, particularly in advanced-stage tumors and lymph node metastatic lesions. Functional studies revealed that TFEB overexpression enhanced metastatic potential in HCC cell lines, whereas its genetic knockdown substantially suppressed metastatic capacity. Mechanistic investigations identified HNRNPA2B1 as a critical mRNA stabilizer of TFEB, establishing a reciprocally reinforcing feedback loop wherein TFEB transactivated HNRNPA2B1 expression. This autoregulatory circuit drove metastatic progression through coordinated upregulation of pro-metastatic genes, ultimately promoting HCC cell dissemination. These results suggested therapeutic targeting of the TFEB-HNRNPA2B1 axis as a promising strategy for inhibiting liver cancer metastasis.