TM4SF1 promotes the self-renewal of esophageal cancer stem-like cells and is regulated by miR-141

// Lei Xue 1, * , Xiying Yu 2, 3, * , Xingran Jiang 2, 5 , Xin Deng 2, 3 , Linlin Mao 2, 3 , Liping Guo 2, 3 , Jinhu Fan 4 , Qinqxia Fan 1 , Liuxing Wang 1 , Shih-Hsin Lu 2, 3 1 Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China 3 Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Beijing, China 4 Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China 5 Current address: Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China * These authors have contributed equally to this work Correspondence to: Shih-Hsin Lu, email: shlu1212@gmail.com , shlu1212@163.com Liuxing Wang, email: wlx2246@126.com Keywords: cancer stem-like cells, TM4SF1, miR-141, esophageal cancer, ESCC Abbreviations: SP: side population, NSP: none side population, ESCC: esophageal squamous cell carcinoma, FTC: fumitremorgin C Received: June 07, 2016     Accepted: November 22, 2016     Published: December 10, 2016 ABSTRACT Cancer stem-like cells have been identified in primary human tumors and cancer cell lines. Previously we found TM4SF1 gene was highly expressed in side population (SP) cells from esophageal squamous cell carcinoma (ESCC) cell lines, but the role and underlying mechanism of TM4SF1 in ESCC remain unclear. In this study, we observed TM4SF1 was up-regulated but miR-141 was down-regulated in SP cells isolated from ESCC cell lines. TM4SF1 could stimulate the self-renewal ability and carcinogenicity of esophageal cancer stem-like cells, and promote cell invasion and migration. In miR-141 overexpression cells, the expression of TM4SF1 was significantly reduced. We also found that overexpression of miR-141 could abolish the self-renewal ability and carcinogenicity of esophageal cancer stem-like cells and decrease cell invasion and migration by suppressing TM4SF1. Consequently, TM4SF1 is a direct target gene of miR-141. The regulation of TM4SF1 by miR-141 may play an important role in controlling self-renewals of esophageal cancer stem-like cells. It may also promote the development of new therapeutic strategies and efficient drugs to target ESCC stem-like cells.