NOD1 inhibits proliferation and enhances response to chemotherapy via suppressing SRC-MAPK pathway in hepatocellular carcinoma
NOD1 inhibits proliferation and enhances response to chemotherapy via suppressing SRC-MAPK pathway in hepatocellular carcinoma
复制标题
NOD1 通过抑制肝细胞癌中的 SRC-MAPK 通路来抑制增殖并增强化疗反应。
DOI：
10.1007/s00109-019-01868-9
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发表时间：
2019-12-23
影响因子：
4.7
通讯作者：
Han, Lihui
中科院分区：
文献类型：
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作者：
Ma, Xiaomin;Qiu, Yumin;Han, Lihui
NOD 1是一种天然免疫传感器，在抗感染中发挥重要作用。然而，其在癌症中的作用远未阐明，NOD 1是否在肝细胞癌（HCC）的进展中起作用从未报道。在此，我们发现NOD 1在肝细胞癌组织中的表达显著降低，并且NOD 1的过表达显著抑制体内肿瘤的发生。体外实验表明NOD 1通过直接靶向原癌基因SRC，诱导细胞周期阻滞于G1期，从而抑制肝癌细胞的增殖。进一步的研究表明NOD 1通过抑制SRC的活化进而抑制SRC/MAPK轴发挥其抗肿瘤作用。此外，NOD 1通过抑制SRC-MAPK轴显著增强肝癌细胞对化疗的反应在体外和体内。总之，这些数据表明，NOD 1通过抑制SRC-MAPK轴抑制肝细胞癌的增殖并增强对索拉非尼或5-FU治疗的反应。关键信息NOD 1在细胞和动物模型中显着抑制HCC的肿瘤发生。NOD 1通过诱导细胞周期阻滞抑制肝癌细胞增殖。NOD 1通过直接与SRC相互作用，抑制SRC-MAPK轴，发挥抗肝癌作用。NOD 1显著增强肝癌细胞对化疗药物的敏感性。
NOD1 is an innate immune sensor playing an important role in fighting against infection. However, its role in cancer is far from being clarified, and whether NOD1 plays a role in the progression of hepatocellular carcinoma (HCC) has never been reported. Here, we found that NOD1 expression was significantly decreased in hepatocellular carcinoma tissues and overexpression of NOD1 significantly inhibited tumorigenesis in vivo. In vitro experiments demonstrated that NOD1 inhibited proliferation of HCC cells by directly targeting proto-oncogene SRC and inducing cell cycle arrest at G1 phase. Further investigation showed that NOD1 exerted its antitumor effect by inhibiting SRC activation and further suppressing SRC/MAPK axis in hepatocellular carcinoma cells. Moreover, NOD1 dramatically enhanced the response of HCC cells to chemotherapy via inhibition of SRC-MAPK axis both in vitro and in vivo. Collectively, these data indicated that NOD1 suppressed proliferation and enhanced response to sorafenib or 5-FU treatment through inhibiting SRC-MAPK axis in hepatocellular carcinoma. Key messagesNOD1 significantly inhibited tumorigenesis of HCC in cellular and animal models. NOD1 inhibited proliferation of HCC cells by inducing cell cycle arrest. NOD1 exerted its antitumor effect on HCC by directly interacting with SRC and inhibiting SRC-MAPK axis. NOD1 significantly enhanced the chemosensitivity of HCC cells to chemotherapeutic drugs.