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

Shuai Zheng; Ying Yang; Ran Song; Xiaomei Yang; Hua Liu; Qian Ma; Longyan Yang; Ran Meng; Tao Tao; Songlin Wang; Junqi He

doi:10.1016/j.bbrc.2015.03.035

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.

Authors

Shuai Zheng¹, Ying Yang², Ran Song³, Xiaomei Yang³, Hua Liu³, Qian Ma¹, Longyan Yang¹, Ran Meng¹, Tao Tao¹, Songlin Wang⁴, Junqi He⁵

Affiliations

¹ Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
² Core Facilities Center, Capital Medical University, Beijing 100069, China.
³ Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University-Cardiff University Joint Centre for Biomedical Research, Cancer Institute of Capital Medical University, Beijing 100069, China.
⁴ Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China; Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China.
⁵ Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China; Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China. Electronic address: jq_he@ccmu.edu.cn.

PMID: 25783053
DOI: 10.1016/j.bbrc.2015.03.035

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 Mas
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 Mas
Proto-Oncogene Proteins
Receptors, G-Protein-Coupled
Angiotensin I
Proto-Oncogene Proteins c-akt
angiotensin I (1-7)