title: Angiotensin-converting enzyme 2 attenuates the metastasis of non-small cell lung cancer through inhibition of epithelial-mesenchymal transition.
abstract: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS). ACE2 plays a critical counterbalancing role by degrading angiotensin II (Ang II) to Ang 1-7. Recent studies suggest that RAS influences tumor growth and development by its paracrine effects on the tumor microenvironment. Epithelial‑mesenchymal transition (EMT) is now thought to be a process that plays a fundamental role in tumor progression and metastasis. In the present study, we investigated the role of ACE2 in lung cancer metastasis and the mechanism of EMT. This is the first study to elucidate the mechanism through which the overexpression of ACE2 in the A549 lung cancer cell line decreases metastasis formation in vivo and upregulates the expression of E-cadherin both in vitro and in vivo. We also observed the downregulation of vimentin, which supports a role of ACE2 in influencing EMT in lung cancer. Further analysis indicated that ACE2 abrogated the upregulation of TGF-β1-induced EMT markers, such as vimentin and α-smooth muscle actin (αSMA) in vitro in A549 cells. Finally, exposing A549 cells stably expressing ACE2 to DX600, an inhibitor of ACE2, recovered the sensitivity of lung cancer cells to TGF-β1-mediated induction of EMT. Our study demonstrated that ACE2 attenuated the metastasis of lung cancer and may serve as a target for new strategies to inhibit EMT in cancer cells.
authors.affiliation: Respiratory Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China. spriteqian@163.com
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Qian
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Huan-Ying
authors.initials: HY
authors.lastname: Wan
authors.forename: Liang
authors.initials: L
authors.lastname: Fan
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Ni
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiang
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Li
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000556:secondary; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000378:metabolism; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2