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.

中文翻译：

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SHANK1在结肠癌发展中的作用。

SH3和多个锚蛋白重复域蛋白1（SHANK1）属于突触后支架蛋白家族。在这项研究中，我们发现与正常组织相比，SHANK1在结肠癌组织中异常高表达。SHANK1表达低的结肠癌患者预后较好。此外，在人类结肠癌细胞系HCT116和HT29中，SHANK1的表达被敲低，并研究了SHANK1在结肠癌肿瘤发生中的作用。我们的结果表明，敲低SHANK1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显着减少，并且诱导了细胞凋亡。SHANK1被敲低的两种细胞系中的Bax / Bcl-2比率均增加，这是线粒体凋亡途径被触发的信号。另外，我们观察到，敲低SHANK1降低了AKT和mTOR的磷酸化形式的表达。这些数据表明，通过AKT / mTOR信号通路，SHANK1的丧失抑制了HCT116和HT29细胞的活力并诱导了其凋亡。我们的数据显示，SHANK1在结肠癌细胞的生长中起着重要作用，并且可以用作结肠癌治疗的新策略。