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Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391196/ https://www.ncbi.nlm.nih.gov/pubmed/32742477 http://dx.doi.org/10.7150/jca.45712 |
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author | Hu, Hao Luo, Shao-Ju Cao, Zhi-rui Wu, Yingzi Mo, Zhuomao Wang, Yongdan Yu, Ling Chen, Yan Xu, Liang Zhang, Shi-Jun |
author_facet | Hu, Hao Luo, Shao-Ju Cao, Zhi-rui Wu, Yingzi Mo, Zhuomao Wang, Yongdan Yu, Ling Chen, Yan Xu, Liang Zhang, Shi-Jun |
author_sort | Hu, Hao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7391196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-73911962020-07-31 Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal Hu, Hao Luo, Shao-Ju Cao, Zhi-rui Wu, Yingzi Mo, Zhuomao Wang, Yongdan Yu, Ling Chen, Yan Xu, Liang Zhang, Shi-Jun J Cancer Research Paper 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. Ivyspring International Publisher 2020-07-09 /pmc/articles/PMC7391196/ /pubmed/32742477 http://dx.doi.org/10.7150/jca.45712 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Hu, Hao Luo, Shao-Ju Cao, Zhi-rui Wu, Yingzi Mo, Zhuomao Wang, Yongdan Yu, Ling Chen, Yan Xu, Liang Zhang, Shi-Jun Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal |
title | Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal |
title_full | Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal |
title_fullStr | Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal |
title_full_unstemmed | Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal |
title_short | Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal |
title_sort | depressive disorder promotes hepatocellular carcinoma metastasis via upregulation of abcg2 gene expression and maintenance of self-renewal |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391196/ https://www.ncbi.nlm.nih.gov/pubmed/32742477 http://dx.doi.org/10.7150/jca.45712 |
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