Follistatin-like protein 1 interacts with programmed cell death 4 to promote vascular mimicry in hepatocellular carcinoma by activating the PI3K/AKT/mTOR signaling pathway

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is highly prone to recurrence and metastasis after curative treatment. However, the molecular mechanisms governing these post-management setbacks remain largely unknown. Previous studies found that the high expression of follistatin-like protein 1 (FSTL1) in tumors is implicated in recurrence, metastasis, and poor patient prognosis. In this study, we aimed to investigate the role of FSTL1 in HCC. We found that FSTL1 overexpression was positively correlated with vascular mimicry and poor prognosis. In vitro experiments confirmed that the interaction between FSTL1 and programmed cell death 4 (PDCD4) activates epithelial-to-mesenchymal transition and promotes the proliferation, invasion, and migration of liver cancer cells. The protein-protein interaction between FSTL1 and PDCD4 significantly promotes VM as well as the expression of the pro-angiogenic vascular endothelial growth factor by activating AKT/mTOR signaling. Our data suggest that FSTL1 may be a potential target for the treatment of HCC. Implications: Our findings indicate that the protein FSTL1 may be a novel therapeutic target for managing patients with HCC.