Ye Xiaojuan, Zhang Yi, Wang Xiao, Li Yandong, Gao Yong
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Department of Oncology, East Hospital, Dalian Medical University, Shanghai, 200120, China.
IUBMB Life. 2016 Apr;68(4):320-7. doi: 10.1002/iub.1486. Epub 2016 Mar 7.
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.
长链脂酰辅酶A合成酶4（ACSL4）是脂肪酸代谢中的关键酶，对花生四烯酸（AA）有明显偏好。最近的报道表明其在肿瘤发生中起关键作用。然而，在胃癌（GC）中，ACSL4的表达和功能仍不清楚。在本研究中，我们确定ACSL4为GC中的一种潜在肿瘤抑制因子。通过实时PCR和免疫组织化学评估GC样本中ACSL4的表达。结果表明，与相邻的非癌性黏膜对照组织相比，癌组织中ACSL4的mRNA和蛋白水平经常下调。基于细胞的功能分析表明，ACSL4的异位表达抑制细胞生长、集落形成和细胞迁移，而ACSL4的敲低增强了这些作用。在裸鼠模型中，ACSL4的敲低也促进了皮下异种移植瘤在体内的生长。此外，蛋白质印迹分析显示，ACSL4的表达对FAK和P21蛋白水平有显著影响。这些发现表明，ACSL4发挥肿瘤抑制作用，可能是GC的潜在治疗靶点。
