Wang Bin, Qi Xiaolong, Liu Jian, Zhou Rui, Lin Chuang, Shangguan Junjie, Zhang Zhuoli, Zhao Liang, Li Guoxin
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Cancer. 2019 Jan 29;10(4):874-884. doi: 10.7150/jca.27635. eCollection 2019.
The contractile protein MYH9 (non-muscle myosin IIA) is an actin-binding protein that plays a fundamental role in cell adhesion, migration, and division. However, its distinct role in colorectal cancer (CRC) still remains unidentified. In this study, we detected significant MYH9 overexpression in CRC samples compared with paired normal tissues using western blotting and tissue microarray immunohistochemistry (IHC). Moreover, analysis of patient clinical information demonstrated that MYH9 overexpression was strongly correlated with lymph node metastasis and poor overall survival. Endogenous overexpression of MYH9 enhanced the ability of cell proliferation and migration , and accelerated CRC growth in mouse models. Silencing of MYH9 revealed repressive effects on CRC cells and . Furthermore, primary biomechanics that involved MAPK/AKT signaling mediated epithelial-mesenchymal transition (EMT) was uncovered underlying MYH9 dependent cell behaviors. Collectively, our data showed that MYH9 significantly promoted tumorigenesis by regulating MAPK/AKT signaling, and was remarkably correlated with poor prognosis in CRC. MYH9 may thus be a novel biomarker and drug target in the diagnosis and treatment of CRC.
收缩蛋白MYH9（非肌肉肌球蛋白IIA）是一种肌动蛋白结合蛋白，在细胞黏附、迁移和分裂中起重要作用。然而，其在结直肠癌（CRC）中的独特作用仍不明确。在本研究中，我们使用蛋白质免疫印迹法和组织芯片免疫组化（IHC）检测发现，与配对的正常组织相比，CRC样本中MYH9显著过表达。此外，对患者临床信息的分析表明，MYH9过表达与淋巴结转移和总体生存率低密切相关。MYH9的内源性过表达增强了细胞增殖和迁移能力，并加速了小鼠模型中CRC的生长。沉默MYH9对CRC细胞具有抑制作用。此外，发现涉及MAPK/AKT信号介导的上皮-间质转化（EMT）的原发性生物力学是MYH9依赖性细胞行为的基础。总体而言，我们的数据表明，MYH9通过调节MAPK/AKT信号显著促进肿瘤发生，并且与CRC的不良预后显著相关。因此，MYH9可能是CRC诊断和治疗中的一种新型生物标志物和药物靶点。
