title: Tumor-suppressive functions of long-chain acyl-CoA synthetase 4 in gastric cancer.
abstract: Long chain acyl CoA synthetase 4 (ACSL4) is a key enzyme in fatty acid metabolism with marked preference for arachidonic acid (AA). Recent reports have implicated its crucial roles in tumorigenesis. However in gastric cancer (GC), the expression and function of ACSL4 remain unclear. In the present study, we identified ACSL4 as a potential tumor suppressor in GC. The ACSL4 expression in GC samples was evaluated by real-time PCR and immunohistochemistry. The results indicated that the mRNA and protein levels of ACSL4 were frequently downregulated in cancer tissues compared with the adjacent non-cancerous mucosa control tissues. Cell-based functional assays exhibited that ectopic expression of ACSL4 inhibits cell growth, colony formation and cell migration, whereas ACSL4 knockdown enhanced these effects. In a nude mice model, ACSL4 knockdown also promoted subcutaneous xenografts' growth in vivo. Moreover, western blot analysis revealed that ACSL4 expression had a significant effect on FAK and P21 protein level. These findings suggest that ACSL4 plays a tumor-suppressive role and could be a potential therapeutic target in GC.
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Oncology, East Hospital, Dalian Medical University, Shanghai, 200120, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, East Hospital, Dalian Medical University, Shanghai, 200120, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
keywords: cell migration; cell proliferation; focal adhesion kinase; gastric cancer; long-chain acyl-CoA synthetase 4