ANGPTL3 inhibits renal cell carcinoma metastasis by inhibiting VASP phosphorylation

Biochem Biophys Res Commun. 2019 Aug 27;516(3):880-887. doi: 10.1016/j.bbrc.2019.06.120. Epub 2019 Jun 30.

Abstract

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.

Keywords: Angiopoietin-like protein 3; Molecular marker; Renal cell carcinoma; Vasodilator-stimulated phosphoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiopoietin-Like Protein 3
  • Angiopoietin-like Proteins / genetics*
  • Angiopoietin-like Proteins / metabolism
  • Animals
  • Atlases as Topic
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Mice, Nude
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Array Analysis
  • Signal Transduction
  • Survival Analysis
  • Tumor Burden

Substances

  • ANGPTL3 protein, human
  • Angiopoietin-Like Protein 3
  • Angiopoietin-like Proteins
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein