Research Papers:

EDG2 enhanced the progression of hepatocellular carcinoma by LPA/PI3K/AKT/ mTOR signaling

Meng Xu, Zhikui Liu, Cong Wang, Bowen Yao and Xin Zheng _

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Oncotarget. 2017; 8:66154-66168. https://doi.org/10.18632/oncotarget.19825

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Meng Xu1,*, Zhikui Liu1,*, Cong Wang1,*, Bowen Yao1 and Xin Zheng1

1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China

*Co-first author

Correspondence to:

Xin Zheng, email: [email protected]

Keywords: EDG2, HCC, post-surgical prognosis, PI3K/AKT/mTOR, EMT

Received: April 28, 2017    Accepted: June 28, 2017    Published: August 02, 2017


HCC is the leading type of the malignant liver tumors with the unsatisfied prognosis. Liver resection has been considered as the predominant curative therapy, however, the post-surgical prognostic evaluation remains an urgent problem and the mechanism of HCC metastases has not been understood completely. EDG2 has been found to accelerate tumor progression through mediating different cell pathways, however, it remains unclear about the role of EDG2 on hepatocarcinogenesis. Here, EDG2 expression was found increased notably in HCC tissues by immunohistochemistry compared with adjacent liver tissues and comparison of survival curves revealed that EDG2 upregulation in HCC tissues was associated with the worse prognosis after liver resection. The positive correlation between EDG2 up-regulation and EMT was observed in HCC samples. Furthermore, EDG2 over-expression in HCC cells brought the typical EMT characteristics including up-regulation of Vimentin, Fibronectin and N-cadherin, suppression of E-cadherin, and enhanced cell migration and invasion capacities. Knockdown of EDG2 reversed the EMT phenotype in HCC cells. The in vivo experiments also identified the oncogenic role of EDG2 on HCC growth. The mechanistic studies elucidated that EDG2 enhanced mTOR phosphorylation via PI3K/AKT signaling and consequently induced EMT of HCC cells. Moreover, EDG2 was found to promote cell viability and proliferation of HCC cell through PI3K/AKT/mTOR/Skp2/p27Kip1 signaling. Taken together, the data here demonstrated EDG2 was a potential predictor for HCC patients receiving liver resection and accelerated HCC progression via regulating EMT driven by PI3K/AKT/mTOR signaling.

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