Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal
Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal
复制标题
抑郁症通过上调 ABCG2 基因表达和维持自我更新促进肝细胞癌转移
DOI：
10.7150/jca.45712
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Zhang, Shi-Jun
中科院分区：
文献类型：
--
作者：
Hu, Hao;Luo, Shao-Ju;Zhang, Shi-Jun
抑郁障碍(DD)是世界范围内导致残疾的主要原因，也是最普遍的情绪障碍。流行病学研究的累积证据表明，DD是癌症的危险因素。然而，DD在肝细胞癌中的作用及其分子机制尚不清楚。在这项研究中，30只小鼠被随机分为两组：肝细胞癌组和肝细胞癌-DD组。采用利血平隔日灌胃，每月注射二乙基亚硝胺(DEN)的方法建立DD小鼠肝癌模型。所有的分子研究都建立在原代细胞培养的基础上，通过集落形成、伤口愈合和球体培养实验来确定DD对肝癌细胞增殖和迁移以及肿瘤干细胞(CSC)自我更新的影响。我们发现CSC标记物ABCG2和CD133在肝细胞癌-DD原代细胞中较肝癌原代细胞上调。此外，在转移和自我更新方面，肝细胞癌-DD原代细胞比肝癌原代细胞更具侵袭性。进一步的研究表明，DD通过激活AKT信号通路促进肿瘤生长和转移，随后ABCG2表达增加。综上所述，我们的新发现表明，DD通过上调AKT途径中的ABCG2来促进增殖、自我更新和转移。
Depressive disorder (DD) is the leading cause of disability worldwide and is the most prevalent mood disorder. Accumulative evidence from epidemiological studies has shown that DD is a risk factor for cancer. However, the role and molecular mechanism of DD in hepatocellular carcinoma (HCC) are still unknown. In this study, 30 mice were randomly divided into two groups: the HCC group and the HCC-DD group. The DD mouse model of HCC was established by induction with reserpine every other day and with monthly doses of diethylnitrosamine (DEN). All of the molecular studies were based on primary cell culture, and the effects of DD on HCC cell proliferation and migration and cancer stem cell (CSC) self-renewal were determined by colony formation, wound healing, and sphere culture assays. We found that the CSC markers ABCG2 and CD133 were upregulated in HCC-DD primary cells compared with HCC primary cells. Moreover, HCC-DD primary cells were more aggressive in terms of metastasis and self-renewal than HCC primary cells. Further study revealed that DD promoted tumor growth and metastasis by activating the AKT signaling pathway followed by an increased ABCG2 expression. Taken together, our novel findings indicate that DD promotes proliferation, self-renewal, and metastasis by upregulating ABCG2 in the AKT pathway.