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KIAA1522 overexpression promotes tumorigenicity and metastasis of esophageal cancer cells through potentiating the ERK activity

Authors Xie ZH, Yu J, Shang L, Zhu YQ, Hao JJ, Cai Y, Xu X, Zhang Y, Wang MR

Received 25 May 2017

Accepted for publication 6 July 2017

Published 26 July 2017 Volume 2017:10 Pages 3743—3754

DOI https://doi.org/10.2147/OTT.S142610

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai

Zhi-Hui Xie, Jing Yu, Li Shang, Yi-Qing Zhu, Jia-Jie Hao, Yan Cai, Xin Xu, Yu Zhang, Ming-Rong Wang

State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China

Abstract: Esophageal squamous cell carcinoma (ESCC) is a highly malignant tumor associated with a poor prognosis, and the molecular mechanisms underlying its formation and progression remain poorly understood. KIAA1522 is upregulated in various tumor tissues, but its function is unknown. Alterations in KIAA1522 expression and its implication in ESCC are currently unclear. In this study, an immunohistochemical analysis of ESCC tissues showed that KIAA1522 was highly expressed in 46% (157/342) of ESCC specimens and that its expression was inversely correlated with the degree of differentiation (P=0.03). Furthermore, small interfering RNA-mediated silencing of KIAA1522 revealed that overexpression of this protein reinforced malignant cell proliferation and anoikis resistance of ESCC cells in vitro. More importantly, KIAA1522 depletion significantly suppressed the growth of ESCC xenograft tumors and lung metastasis of ESCC cells in nude mice. At the molecular level, inhibition of KIAA1522 expression markedly reduced the phosphorylated extracellular signal-regulated kinase (ERK) levels in both suspended and adherent ESCC cells, suggesting that KIAA1522 might promote cell proliferation and survival via the ERK cascade. Taken together, these data suggest that upregulation of KIAA1522 might enhance tumorigenicity and metastasis of ESCC cells through potentiating the ERK activity. Thus, aberrant expression of KIAA1522 plays oncogenic roles in ESCC and might serve as a novel molecular target in ESCC treatment.

Keywords: esophageal squamous cell carcinoma, KIAA1522, tumor growth, anoikis, metastasis, extracellular signal-regulated kinase

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