AKIP1 promoted epithelial-mesenchymal transition of non-small-cell lung cancer via transactivating ZEB1.

Autor:	Guo X; Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's HospitalZhengzhou 450000, Henan, China., Zhao L; Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's HospitalZhengzhou 450000, Henan, China., Cheng D; Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's HospitalZhengzhou 450000, Henan, China., Mu Q; Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's HospitalZhengzhou 450000, Henan, China., Kuang H; Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's HospitalZhengzhou 450000, Henan, China., Feng K; Department of Respiratory Disease, Henan Provincial People's Hospital, Zhengzhou University People's HospitalZhengzhou 450000, Henan, China.
Jazyk:	angličtina
Zdroj:	American journal of cancer research [Am J Cancer Res] 2017 Nov 01; Vol. 7 (11), pp. 2234-2244. Date of Electronic Publication: 2017 Nov 01 (Print Publication: 2017).
Abstrakt:	Non-small-cell lung cancer (NSCLC) is one of the leading death-related malignancies worldwide with elusive molecular mechanisms. A-kinase interacting protein 1 (AKIP1) is an important regulator controlling metastasis, lymphangiogenesis and angiogenesis. However, the role of AKIP1 in NSCLC progression is still little known. Here, we found that AKIP1 was overexpressed in NSCLC specimens as well as cell lines. Overexpression of AKIP1 in NSLCC tissues was positively correlated with TNM stage, lymph node metastasis and poor prognosis. Knockdown of AKIP1 inhibited NSCLC cell migration, invasion and epithelial-mesenchymal transition (EMT), as indicated by the up-regulation of mesenchymal markers (fibronectin and vimentin) and down-regulation of epithelial marker E-cadherin, whereas overexpression of AKIP1 showed the opposite effects. Moreover, AKIP1 transactivated Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression via directly binding to ZEB1 promoter, thereby leading to E-cadherin transcriptional repression. Additionally, we observed that the binding efficiency of AKIP1 within ZEB1 promotor was determined by the interaction between AKIP1 and SP1. In conclusion, AKIP1 promoted EMT of NSCLC via transactivating ZEB1, suggesting AKIP1 as a potential therapeutic target. Competing Interests: None.
Databáze:	MEDLINE
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