Lamp2 inhibits epithelial-mesenchymal transition by suppressing Snail expression in HCC

Abstract

// Hao Zheng 1, * , YuanYang 1, * , Chen Ye 3, * , Peng-Peng Li 1 , Zhen-Guang Wang 1 , Hao Xing 1 , Hao Ren 2 and Wei-Ping Zhou 1 1 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China 2 Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China 3 Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China * These authors contributed equally to this work Correspondence to: Wei-Ping Zhou, email: ehphwp@126.com Hao Ren, email: hmren@yahoo.com Keywords: Lamp2; hepatocellular carcinoma; EMT; metastasis Received: April 28, 2017      Accepted: November 10, 2017      Published: July 13, 2018 ABSTRACT Lysosomal associated membrane protein 2 (Lamp2) influences a broad range of physiological and pathological processes. However, little is known about the role of Lamp2 in hepatocellular carcinoma (HCC) metastasis. This study found that Lamp2 expression was significantly lower in HCC tissues than in adjacent nontumor tissues (ANTs), and its expression level correlated with HCC metastasis. Low Lamp2 expression was significantly correlated with the AFP serum level (> 20 ng/Ml, P = 0.024), capsular formation (absent, P = 0.024), and microvascular invasion (present, P < 0.001), and low expression of Lamp2 indicated a poor prognosis in HCC. LowLamp2 expression was an independent and significant risk factor for recurrence-free survival (RFS; P < 0.001) and overall survival (OS; P < 0.001) in HCC. In this study, we demonstrated that Lamp2 overexpression inhibited cell motility and invasiveness in vitro and inhibited lung metastasis in vivo . In addition, Lamp2 could reverse the EMT program. Lamp2 silencing by siRNA in HCC cell lines enhanced the expression of mesenchymal markers and decreased the expression of epithelial markers. Consistent with these findings, Lamp2 overexpression had the opposite effects. Mechanistically, we found that Lamp2 could suppress Snail expression, upregulate E-cadherin, and inhibit HCC cell epithelial-mesenchymal transition (EMT).Together, these findings suggest that Lamp2 attenuates EMT by suppressing Snail expression in HCC.