Angiopoietin-like 4 enhances metastasis and inhibits apoptosis via inducing bone morphogenetic protein 7 in colorectal cancer cells

Biochem Biophys Res Commun. 2015 Nov 6;467(1):128-34. doi: 10.1016/j.bbrc.2015.09.104. Epub 2015 Sep 28.

Abstract

Angiopoietin-like 4 (ANGPTL4), a secretory glycoprotein, plays an important role in cancer metastasis. In the present study, we aim to investigate the roles and mechanisms of ANGPTL4 in the regulation of colorectal cancer metastasis. We found that expression level of ANGPTL4 was increased in colorectal cancer tissues, compared with that in normal tissues. Moreover, liver metastasis was significantly associated with higher expression of ANGPTL4. In vitro studies further showed that overexpression of ANGPTL4 enhanced cell migration, invasion and inhibited apoptosis. At the molecular level, ANGPTL4 overexpression resulted in an up-regulation of bone morphogenetic protein 7 (BMP7). Indeed, knockdown of BMP7 by small interfering RNA (siRNA) oligos reversed the roles of ANGPTL4 overexpression in HCT116 cells. Finally, in vivo studies further confirmed the metastatic roles of ANGPTL4 by inducing BMP7. Therefore, our study demonstrated that ANGPTL4 might promote metastasis and might inhibit apoptosis of colorectal cancer cells by up-regulation of BMP7.

Keywords: ANGPTL4; Apoptosis; BMP7; Colorectal cancer; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-Like Protein 4
  • Angiopoietins / genetics*
  • Apoptosis / genetics
  • Bone Morphogenetic Protein 7 / antagonists & inhibitors
  • Bone Morphogenetic Protein 7 / biosynthesis*
  • Bone Morphogenetic Protein 7 / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Up-Regulation

Substances

  • ANGPTL4 protein, human
  • Angiopoietin-Like Protein 4
  • Angiopoietins
  • BMP7 protein, human
  • Bone Morphogenetic Protein 7