BIF-1 expression in human cancers: roles in apoptosis, autophagy, and therapeutic potential

Bax-interacting factor-1 (BIF-1), also known as endophilin B1 (SH3GLB1), is a membrane-associated protein involved in apoptosis, autophagy, and membrane dynamics. There is growing evidence of a context-dependent role in tumor biology, mainly associated with tumor-suppressive functions in several cancers. In this narrative review, we summarize current evidence regarding BIF-1 expression patterns and its functional relevance in cancer-related pathways. Downregulation of BIF-1 has been consistently reported in melanoma, breast cancer, prostate cancer, gastric carcinoma, colorectal cancer, urinary bladder cancer and gallbladder cancer, where reduced expression is associated with impaired apoptosis, altered autophagy and tumor progression, supporting its potential value as a tumor suppressor-associated biomarker. On the other hand, hepatocellular carcinoma shows a context-dependent expression pattern and inconsistent associations with clinical outcomes. Its clinical utility in these tumors is limited because diagnostic and prognostic significance has not been consistently demonstrated. Therapeutic studies suggest that modulation of BIF-1-related pathways could influence autophagy, apoptosis and cellular metabolism, implying indirect participation in cancer treatment strategies. In general, BIF-1 seems to be a potential biomarker linked to tumor suppression in various epithelial cancers, especially in melanoma, breast, and prostate cancers. However, it's clinical utility remains limited or appears variable in pancreatic ductal adenocarcinoma and Merkel cell carcinoma. These findings highlight the context-dependent role of BIF-1 in tumor biology.