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结肠癌转移相关蛋白1(MACC1)在癌症中的潜在治疗应用及预后意义

The potential therapeutic applications and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) in cancers.

作者信息

Kopczyńska Ewa Katarzyna

机构信息

Department of Pathobiochemistry and Clinical Chemistry, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poland.

出版信息

Contemp Oncol (Pozn). 2016;20(4):273-80. doi: 10.5114/wo.2016.61846. Epub 2016 Sep 5.

Abstract

The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009. Expression of MACC1 was found to be significantly upregulated in primary and metastatic colon carcinomas compared to normal tissues or adenomas. The induction of MACC1 occurs at the crucial step of transition from a benign to a malignant phenotype. The aim of this review was to summarise current results of non-clinical and clinical studies on the role of MACC1 in the carcinogenesis and progression of cancer, as well its potential therapeutic and prognostic significance. The gene encoding the HGF receptor MET is a transcriptional target of MACC1. In addition to promoting the proliferation, invasion, and migration of colon cancer cells in cell culture and tumour growth and metastasis in mouse models, MACC1 also contributes to carcinogenesis and progression of colorectal cancer through the β-catenin signalling pathway and mesenchymal-epithelial transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of different types of cancer. MACC1 is a promising therapeutic target for antitumour and antimetastatic intervention strategies for cancers. Here, it is presented as a potential independent prognostic indicator of reduced overall survival as well as of the occurrence of distant metastasis in patients with different types of cancer.

摘要

结肠癌转移相关基因1(MACC1)于2009年被发现。与正常组织或腺瘤相比,原发性和转移性结肠癌中MACC1的表达显著上调。MACC1的诱导发生在从良性表型向恶性表型转变的关键步骤。本综述的目的是总结关于MACC1在癌症发生和进展中的作用及其潜在治疗和预后意义的非临床和临床研究的当前结果。编码肝细胞生长因子受体MET的基因是MACC1的转录靶点。除了在细胞培养中促进结肠癌细胞的增殖、侵袭和迁移以及在小鼠模型中促进肿瘤生长和转移外,MACC1还通过β-连环蛋白信号通路和间充质-上皮转化促进结直肠癌的发生和进展。在不同类型癌症的细胞系中研究了用si/sh RNA敲低MACC1。MACC1是癌症抗肿瘤和抗转移干预策略的一个有前景的治疗靶点。在此,它被视为不同类型癌症患者总生存期缩短以及远处转移发生的潜在独立预后指标。

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