The roles of SHANK1 in the development of colon cancer
The roles of SHANK1 in the development of colon cancer
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DOI：
10.1002/cbf.3529
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发表时间：
2020-04-30
影响因子：
3.6
通讯作者：
Liu, Guoqin
中科院分区：
文献类型：
--
作者：
Wang, Lei;Lv, Ying;Liu, Guoqin
SH 3和多锚蛋白重复结构域蛋白1（SHANK 1）属于突触后支架蛋白家族。在这项研究中，我们发现SHANK 1在结肠癌组织中的表达比正常组织高得多。SHANK 1低表达的结肠癌患者预后较好。此外，SHANK 1在人结肠癌细胞系HCT 116和HT 29中的表达被敲低，并且研究了SHANK 1在结肠癌肿瘤发生中的作用。我们的结果表明，SHANK 1的敲低抑制了两种细胞的存活和增殖。与对照细胞相比，这两种细胞系的迁移能力显著降低，并诱导凋亡。SHANK 1被敲低的两种细胞系中的Bax/Bcl-2比率增加，这是线粒体凋亡途径被触发的信号。此外，我们观察到SHANK 1的敲低降低了AKT和mTOR的磷酸化形式的表达。这些数据表明，SHANK 1的缺失通过AKT/mTOR信号通路抑制HCT 116和HT 29细胞的活力并诱导细胞凋亡。SHANK 1在结肠癌细胞的生长过程中起重要作用，可能成为结肠癌治疗的新策略。研究意义本文报道了SHANK 1在结肠癌组织中异常高表达，并与患者预后不良相关。此外，SHANK 1的敲低通过AKT/mTOR信号通路抑制结肠癌细胞系的活力并诱导细胞凋亡。提示SHANK 1可能是一个新的结肠癌癌基因。这项研究揭示了SHANK 1在神经元发育和认知发育中的作用。它为结肠癌的预测和治疗提供了一个新的潜在靶点。
SH3 and multiple ankyrin repeat domains protein 1 (SHANK1) belongs to a family of postsynaptic scaffolding proteins. In this study, we found that SHANK1 was abnormally high expressed in colon cancer tissues compared to normal tissues. Colon cancer patients with low SHANK1 expression had better prognosis. Furthermore, the expression of SHANK1 was knocked down in human colon cancer cell lines HCT116 and HT29 and the role of SHANK1 was investigated in colon cancer tumorigenesis. Our results showed that the knockdown of SHANK1 inhibited the survival and proliferation of both cells. The migration of these two cell lines was significantly reduced and the apoptosis was induced compared with control cells. The Bax/Bcl-2 ratio in both cell lines that SHANK1 was knocked down was increased, which is a signal that the mitochondrial apoptotic pathway was triggered. In addition, we observed that knockdown of SHANK1 reduced the expression of phosphorylated forms of AKT and mTOR. These data suggested that loss of SHANK1 inhibited viability and induced apoptosis of HCT116 and HT29 cells through the AKT/mTOR signaling pathway. Our data revealed that SHANK1 played important roles in the growth of colon cancer cells and may be used as a novel strategy for colon cancer therapy.Significance of the study Herein, we reported that SHANK1 was abnormally high expressed in colon cancer tissues and associated with worse prognosis of patients. In addition, knockdown of SHANK1 inhibited viability and induced apoptosis in colon cancer cell lines through AKT/mTOR signaling pathways. These data suggest that SHANK1 may be a new oncogene in colon cancer. This study reveals the role of SHANK1 in addition to neuronal development and cognitive development. And it provides a new potential target for the prediction and treatment of colon cancer.