Lysophosphatidic acid mediated PI3K/Akt activation contributed to esophageal squamous cell cancer progression
Lysophosphatidic acid mediated PI3K/Akt activation contributed to esophageal squamous cell cancer progression
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DOI：
10.1093/carcin/bgaa143
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发表时间：
2021-04-01
期刊：
影响因子：
4.7
通讯作者：
Zhu, Shengtao
中科院分区：
文献类型：
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作者：
Liu, Si;Jiang, Haiyan;Zhu, Shengtao
溶血磷脂酸（LPA）及其G蛋白偶联受体（Lpa 1-Lpa 6）介导与癌症生长和进展相关的多种活动。然而，关于LPA是否以及如何促进食管鳞状细胞癌（ESCC）的发生尚无系统的研究。在这里，我们表明，自分泌运动因子（ATX），主要LPA产生酶，是高表达的ESCC，和过度表达ATX与ESCC患者的不良后果。同时，Lpar 1在ESCC细胞中的表达明显高于Het-1a（人食管正常上皮细胞）。功能实验表明，LPA能显著促进食管鳞癌细胞的增殖和迁移。此外，Lpar 1敲低取消了LPA对ESCC细胞增殖和迁移的影响。LPA通过PI 3 K/Akt信号通路促进食管鳞癌细胞增殖和迁移。用Lpar 1抑制剂BMS-986020处理KYSE 30细胞异种移植物显著抑制肿瘤生长。我们的研究结果揭示了LPA在ESCC中的重要作用，Lpar 1可能是ESCC的潜在治疗靶点。
Lysophosphatidic acid (LPA) and its G-protein-coupled receptors (Lpar1-Lpar6) mediate a plethora of activities associated with cancer growth and progression. However, there is no systematic study about whether and how LPA promotes esophageal squamous cell carcinoma (ESCC). Here, we show that autotaxin (ATX), a primary LPA-producing enzyme, is highly expressed in ESCC, and overexpressed ATX is associated with the poor outcome of ESCC patients. Meanwhile, the expression of Lpar1 was much higher in ESCC cells compared with Het-1a (human esophagus normal epithelial cells). Functional experiments showed that LPA remarkably increased the proliferation and migration of ESCC cells. Furthermore, Lpar1 knockdown abolished the effect of LPA on ESCC cell proliferation and migration. Mechanistic studies revealed that LPA promoted ESCC cell lines proliferation and migration through PI3K/Akt pathway. Treatment of KYSE30 cell xenografts with Lpar1 inhibitor BMS-986020 significantly repressed tumor growth. Our results shed light on the important role of LPA in ESCC, and Lpar1 might be a potential treatment target for ESCC.