Carcinogenesis. 2019 Sep 27. pii: bgz156. doi: 10.1093/carcin/bgz156. [Epub ahead of print]
Wang B1, Zheng J1, Chen Q1, Wu C1, Li Y2, Yu XY3, Liu B4, Liang C5, Liu SB6, Ding H1, Wang S1, Xue T1, Song D1, Lei Z1, Amin HM7, Song YH1, Zhou J8.
Author Information
1Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, P. R. China.
2Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
3Key Laboratory of Molecular Clinical Pharmacology and Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
4Department of Cardiology, Second Hospital of Jilin University, Changchun, Jilin, P. R. China.
5Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P. R. China.
6Suzhou Vocational Health College, Suzhou Key Laboratory of Biotechnology for Laboratory Medicine, Suzhou, Jiangsu Province, China.
7Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
8Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, P. R. China.
Abstract
CLIC4 has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by Western blot and RT-PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared to adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells，which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared to N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44, OCT4, and inhibited migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.