title: Therapeutic inhibition of phospholipase D1 suppresses hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) represents a leading cause of deaths worldwide. Novel therapeutic targets for HCC are needed. Phospholipase D (PD) is involved in cell proliferation and migration, but its role in HCC remains unclear. In the present study, we show that PLD1, but not PLD2, was overexpressed in HCC cell lines (HepG2, Bel-7402 and Bel-7404) compared with the normal human L-02 hepatocytes. PLD1 was required for the proliferation, migration and invasion of HCC cells without affecting apoptosis and necrosis, and PLD1 overexpression was sufficient to promote those effects. By using HCC xenograft models, we demonstrated that therapeutic inhibition of PLD1 attenuated tumour growth and epithelial-mesenchymal transition (EMT) in HCC mice. Moreover, PLD1 was found to be highly expressed in tumour tissues of HCC patients. Finally, mTOR (mechanistic target of rapamycin) and Akt (protein kinase B) were identified as critical pathways responsible for the role of PLD1 in HCC cells. Taken together, the present study indicates that PLD1 activation contributes to HCC development via regulation of the proliferation, migration and invasion of HCC cells, as well as promoting the EMT process. These observations suggest that inhibition of PLD1 represents an attractive and novel therapeutic modality for HCC.
authors.affiliation: Regeneration and Ageing Lab, Experimental Centre of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China changqingyang_tj@hotmail.com junjiexiao@shu.edu.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Regeneration and Ageing Lab, Experimental Centre of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Regeneration and Ageing Lab, Experimental Centre of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bei
authors.affiliation: Department of Pathology, Gansu Provincial Hospital, Lanzhou 730000, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Regeneration and Ageing Lab, Experimental Centre of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China Department of Experimental Biochemistry and Physiology, Faculty of Natural Sciences and Mathematics, University Ss Cyril and Methodius, 1000 Skopje, Republic of Macedonia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Dimitrova-Shumkovska
authors.affiliation: Regeneration and Ageing Lab, Experimental Centre of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.
authors.forename: Dongchao
authors.initials: D
authors.lastname: Lv
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Meiyi
authors.initials: M
authors.lastname: Song
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China changqingyang_tj@hotmail.com junjiexiao@shu.edu.cn.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008810:Mice, Inbred C57BL; D010739:Phospholipase D / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010739:Phospholipase D; C106801:phospholipase D1
keywords: hepatocellular carcinoma; invasion; migration; phospholipase D1; proliferation