ANGPTL3 inhibits renal cell carcinoma metastasis by inhibiting VASP phosphorylation

Angiopoietin-like proteins (ANGPTLs) comprise a group of proteins that are structurally similar to angiopoietins. In our previous studies, we found that ANGPTL3 can inhibit sorafenib resistance in renal cell carcinoma (RCC). According to bioinformatics analysis based on data in the Cancer Genome Atlas (TCGA), we found that expression of ANGPTL3 was significantly lower in RCC tissues than in adjacent tissues and that disease-free survival and overall survival were significantly shorter in patients with lower ANGPTL3 levels than in those with higher ANGPTL3 levels. Consistent with these results, we demonstrated that RCC tissues exhibited lower ANGPTL3 mRNA and protein expression levels than paired adjacent tissues. Moreover, we found that ANGPTL3 upregulation was associated with better clinical outcomes in RCC patients. ANGPTL3 overexpression inhibited the metastatic ability in RCC cells. Mechanistically, ANGPTL3 binds to vasodilator-stimulated phosphoprotein (VASP) and inhibits its phosphorylation at amino acid 157 in RCC cells. Finally, ANGPTL3 expression and VASP-157 phosphorylation may be combined to predict the prognosis of RCC patients. Overall, our findings describe the role of ANGPTL3 in inhibiting RCC metastasis and thus provide new molecular markers for RCC treatment and prognosis.