Tspan5 is an independent favourable prognostic factor and suppresses tumour growth in gastric cancer
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Peirong He1,2,*, Suihai Wang1,*, Xuefeng Zhang1, Yanjun Gao1, Wenbo Niu1, Ningning Dong1, Xiangyi Shi1, Yan Geng2, Qiang Ma1, Ming Li1, Bo Jiang2, Ji-Liang Li1,3
1School of Biotechnology, Southern Medical University, Guangzhou 510515, China
2Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
3Institute of Translational and Stratified Medicine, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, U.K
*These authors have contributed equally to this work
Bo Jiang, e-mail: firstname.lastname@example.org
Ji-Liang Li, e-mail: email@example.com
Keywords: gastric cancer, tetraspanin, tumour suppressor, cell cycle, biomarker
Received: February 27, 2016 Accepted: April 26, 2016 Published: May 20, 2016
Tetraspanins are believed to interact with specific partner proteins forming tetraspanin-enriched microdomains and regulate some aspects of partner protein functions. However, the role of Tspan5 during pathological processes, particularly in cancer biology, remains unknown. Here we report that Tspan5 is significantly downregulated in gastric cancer (GC) and closely associated with clinicopathological features including tumour size and TNM stage. The expression of Tspan5 is inversely correlated with patient overall survival and is an independent prognostic factor in GC. Upregulation of Tspan5 in tumour cells results in inhibition of cell proliferation and colony formation in vitro and suppression of xenograft growth of GC by reducing tumour cell proliferation in vivo. Thus, Tspan5 functions as a tumour suppressor in stomach to control the tumour growth. Mechanistically, Tspan5 inhibits the cell cycle transition from G1-S phase by increasing the expression of p27 and p15 and decreasing the expression of cyclin D1, CDK4, pRB and E2F1. The correlation of Tspan5 expression with the expression of p27, p15, cyclin D1, CDK4, pRB and E2F1 in vivo are also revealed in xenografted tumours. Reconstitution of either cyclin D1 or CDK4 in Tspan5-overexpressing GC cells rescues the inhibitory phenotype produced by Tspan5, suggesting that cyclin D1/CDK4 play a dominant role in mediating the suppression of tumour growth by Tspan5 in GC. Our results suggest that Tspan5 may serve as a prognostic biomarker for predicting outcome of GC patients and provide new insights into the pathogenesis of GC and rational for the development of clinical intervention strategies against GC.
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