Li Zhaodong, Tang Yongyao, Cai Jing, Wu Shunlong, Song Fangzhou
Molecular Medicine and Cancer Research Center, Chongqing Medical University, 1#Yixue Yuan Road, Yuzhong District, Chongqing 400016, China.
Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Life (Basel). 2022 Sep 5;12(9):1381. doi: 10.3390/life12091381.
MAGUK p55 scaffold protein 7 (MPP7) is a member of the stardust family of membrane-associated guanosine kinase protein P55 and plays a role in the establishment of epithelial cell polarity. However, its potential implication in human esophageal cancer is unclear. In this study, we investigated the expression profile of MPP7 and its functional impact on esophagus cancer. Expression analyses of immunohistochemical microarrays with survival and prognostic information of 103 patients with esophageal cancer demonstrated that MPP7 was overexpressed in 52 patients, who showed poor survival rates. The transcriptional expression of MPP7 in esophageal cancer in TCGA database increased successively from normal epithelial, to esophageal adenocarcinoma, to esophageal squamous cell carcinoma. Transcriptome sequencing after MPP7 knockdown in esophageal carcinoma cells showed that wound-healing-associated proteins were down-regulated, and the TGF-β pathway was one of the important signaling pathways. A loss-of-function study showed that the knockdown of MPP7 inhibited cell migration and invasion. These results could be verified in a model of tumor cells injected into the tail vein and subcutaneous tumor of nude mice. Herein, our results indicated that MPP7 could have an oncogenic role in human esophagus cancer, thus demonstrating its potential as a novel biomarker for the diagnosis and/or treatment of esophagus cancer.
膜相关鸟苷激酶蛋白P55星尘家族成员MAGUK p55支架蛋白7(MPP7)在上皮细胞极性建立中发挥作用。然而,其在人类食管癌中的潜在影响尚不清楚。在本研究中,我们调查了MPP7的表达谱及其对食管癌的功能影响。对103例食管癌患者进行免疫组织化学微阵列表达分析并结合生存和预后信息,结果显示52例患者MPP7过表达,这些患者生存率较低。TCGA数据库中食管癌MPP7的转录表达从正常上皮组织到食管腺癌再到食管鳞状细胞癌依次升高。食管癌细胞中MPP7敲低后的转录组测序表明,与伤口愈合相关的蛋白下调,转化生长因子-β(TGF-β)途径是重要的信号通路之一。功能丧失研究表明,MPP7敲低抑制细胞迁移和侵袭。这些结果在将肿瘤细胞注入裸鼠尾静脉和皮下肿瘤的模型中得到验证。在此,我们的结果表明MPP7可能在人类食管癌中发挥致癌作用,从而证明其作为食管癌诊断和/或治疗新生物标志物的潜力。