Ang-(1-7) promotes the migration and invasion of human renal cell carcinoma cells via Mas-mediated AKT signaling pathway

Biochem Biophys Res Commun. 2015 May 1;460(2):333-40. doi: 10.1016/j.bbrc.2015.03.035. Epub 2015 Mar 14.

Abstract

Ang-(1-7) is an active peptide component of renin-angiotensin system and endogenous ligand for Mas receptor. In the current study, we showed that Ang-(1-7) enhanced migratory and invasive abilities of renal cell carcinoma cells 786-O and Caki-1 by wound-healing, transwell migration and transwell invasion assays. Mas antagonist A779 pretreatment or shRNA-mediated Mas knockdown abolished the stimulatory effect of Ang-(1-7). Furthermore, Ang-(1-7)-stimulated AKT activation was inhibited by either A779 pretreatment or Mas knockdown. Blockage of AKT signaling by AKT inhibitor VIII inhibited Ang-(1-7)-induced migration and invasion in 786-O cells. Taken together, our results provided the first evidence for the pro-metastatic role of Ang-(1-7) in RCC, which may help to better understand the molecular mechanism underlying the progression of this tumor.

Keywords: AKT signaling; Angiotensin-(1-7); Invasion; Mas receptor; Migration; Renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis*
  • Peptide Fragments / pharmacology*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects*
  • Wound Healing

Substances

  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • proto-oncogene proteins c-mas-1
  • Angiotensin I
  • Proto-Oncogene Proteins c-akt
  • angiotensin I (1-7)