Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma
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Zhuan Lv1,*, Jane J. Yu2,*, Wei-Jie Zhang1, Li Xiong3, Feng Wang1, Li-Feng Li1, Xue-Liang Zhou1, Xin-Ya Gao1, Xian-Fei Ding1, Li Han1, Ya-Fei Cai1, Wang Ma1, Liu-Xing Wang1
1Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
2University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Cincinnati, OH, USA
3Department of General Surgery, The Second Xiang Ya Hospital of Central South University, Hunan, China
*These authors are contributed equally to this work
Liu-Xing Wang, email: firstname.lastname@example.org
Wang Ma, email: email@example.com
Keywords: Lgr5, esophageal squamous cell carcinoma, cancer stem cells, spheroid body cells, small interfering RNA
Received: October 09, 2016 Accepted: January 29, 2017 Published: February 22, 2017
Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated cells with biological characteristics that include the capacity for self-renewal, differentiation into various lineages, and tumor initiation. To explore the mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene of the Wnt signaling pathway, which has been identified as a marker of intestinal stem cells and shown to be overexpressed in several human malignancies. Lgr5 expression was significantly correlated with lymph node metastasis, increased depth of invasion, increased tumor size, advanced differentiation, higher AJCC stage and poorer survival. Silencing of Lgr5 expression in the ESCC cell line KYSE450 by small interfering RNA (siRNA) strongly inhibited cell proliferation, migration and invasion ability, the expression of CSCs-related genes and Wnt/β-catenin signaling. In addition, Lgr5 was highly expressed in ESCC spheroid body cells, which were identified by high expression of CSCs-related genes, and high tumorigenicity in vivo. Taken together, these results demonstrate that Lgr5 activation of Wnt/β-catenin signaling is a potential mechanism to promote the progression of ESCC and ESCC stem cell renewal, and Lgr5 may be used as a molecular target for the development of treatments for ESCC.
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