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AMPK-ERK/CARM1信号通路影响肝癌患者样本中肝细胞的自噬

AMPK-ERK/CARM1 Signaling Pathways Affect Autophagy of Hepatic Cells in Samples of Liver Cancer Patients.

作者信息

Qin Qiu-Fang, Li Xiao-Jun, Li Yu-Sang, Zhang Wei Kevin, Tian Gui-Hua, Shang Hong-Cai, Tang He-Bin

机构信息

Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, China.

Key Laboratory of Chinese Internal Medicine of MOE, Beijing Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Oncol. 2019 Nov 14;9:1247. doi: 10.3389/fonc.2019.01247. eCollection 2019.

Abstract

Liver cancer is one of the most common malignant tumors, with the death rate ranking fourth among all types of cancer. Over the past few decades, several studies have reported that liver tumorigenesis is associated with dysfunction in autophagy. However, the detailed mechanism remains unclear. In this paper, we used tissue micro-array (TMA) of liver cancer to detect proteins associated with the regulation of autophagic signaling in non-cancerous and cancerous regions by immunohistochemical staining. Those proteins contained 4-HNE, p-AMPK, Erk1/2, p-Erk1/2, CARM1, TFEB, LAMP1, and p62. According to the degrees of tumor differentiation in patients (well differentiated group vs. moderately and poorly differentiated group), we analyzed each protein's expression in the ratio of the "cancerous region/non-cancerous region" in two groups. Current data showed that there were AMPK-ERK/CARM1 autophagic signaling pathways during the formation of liver cancer. The above-mentioned changes in signals indicated an upregulation of autophagy in cancerous regions, which means overactivated autophagy plays an important role in liver cancer.

摘要

肝癌是最常见的恶性肿瘤之一,其死亡率在所有癌症类型中排名第四。在过去几十年里,多项研究报告称肝肿瘤发生与自噬功能障碍有关。然而,具体机制仍不清楚。在本文中,我们使用肝癌组织芯片(TMA),通过免疫组化染色检测非癌区域和癌区域中与自噬信号调控相关的蛋白质。这些蛋白质包括4-HNE、p-AMPK、Erk1/2、p-Erk1/2、CARM1、TFEB、LAMP1和p62。根据患者的肿瘤分化程度(高分化组与中低分化组),我们分析了两组中每种蛋白质在“癌区域/非癌区域”比值中的表达情况。目前的数据表明,在肝癌形成过程中存在AMPK-ERK/CARM1自噬信号通路。上述信号变化表明癌区域自噬上调,这意味着过度激活的自噬在肝癌中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a77b/6868028/8a08a3d2faa2/fonc-09-01247-g0001.jpg

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