Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma

Hepatocellular carcinoma (HCC) is one of the most fatal cancers. In almost all populations, males have a higher HCC rate than females. Here we sought to explore the roles and mechanisms of acetylcholine (Ach) and androgen receptor (AR) on regulating the fate determinations of HCC. Ach activated AR a...

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Autores principales: Nie, Huizhen, Cao, Qingzhen, Zhu, Lei, Gong, Yuehua, Gu, Jianren, He, Zuping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631145/
https://www.ncbi.nlm.nih.gov/pubmed/23620780
http://dx.doi.org/10.1371/journal.pone.0061678
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author Nie, Huizhen
Cao, Qingzhen
Zhu, Lei
Gong, Yuehua
Gu, Jianren
He, Zuping
author_facet Nie, Huizhen
Cao, Qingzhen
Zhu, Lei
Gong, Yuehua
Gu, Jianren
He, Zuping
author_sort Nie, Huizhen
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most fatal cancers. In almost all populations, males have a higher HCC rate than females. Here we sought to explore the roles and mechanisms of acetylcholine (Ach) and androgen receptor (AR) on regulating the fate determinations of HCC. Ach activated AR and promoted its expression in HCC cells. Ach enhanced HCC cell migration and invasion but inhibited their apoptosis. Ach had no obvious effects on the migration, invasion, or apoptosis in AR-negative HCC cells. Elevation of migration and invasion induced by Ach was eliminated in AR-knockdown HCC cells. In contrast, Ach stimulated the migration and invasion but suppressed apoptosis in AR over-expressed HCC cells. Additionally, AR agonist R1881 promoted the migration and invasion but reduced the apoptosis of SNU-449 cells, whereas AR antagonist casodex inhibited the migration and invasion but stimulated the apoptosis of SNU-449 cells. STAT3 and AKT phosphorylation was activated by Ach in HCC cells. Collectively, these data suggest that Ach activates STAT3 and AKT pathways and acts on AR to promote the migration and invasion but inhibit the apoptosis of HCC cells. This study thus provides novel insights into carcinogenesis of liver cancer by local interaction between neurotransmitter Ach and hormone receptor AR in HCC.
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spelling pubmed-36311452013-04-25 Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma Nie, Huizhen Cao, Qingzhen Zhu, Lei Gong, Yuehua Gu, Jianren He, Zuping PLoS One Research Article Hepatocellular carcinoma (HCC) is one of the most fatal cancers. In almost all populations, males have a higher HCC rate than females. Here we sought to explore the roles and mechanisms of acetylcholine (Ach) and androgen receptor (AR) on regulating the fate determinations of HCC. Ach activated AR and promoted its expression in HCC cells. Ach enhanced HCC cell migration and invasion but inhibited their apoptosis. Ach had no obvious effects on the migration, invasion, or apoptosis in AR-negative HCC cells. Elevation of migration and invasion induced by Ach was eliminated in AR-knockdown HCC cells. In contrast, Ach stimulated the migration and invasion but suppressed apoptosis in AR over-expressed HCC cells. Additionally, AR agonist R1881 promoted the migration and invasion but reduced the apoptosis of SNU-449 cells, whereas AR antagonist casodex inhibited the migration and invasion but stimulated the apoptosis of SNU-449 cells. STAT3 and AKT phosphorylation was activated by Ach in HCC cells. Collectively, these data suggest that Ach activates STAT3 and AKT pathways and acts on AR to promote the migration and invasion but inhibit the apoptosis of HCC cells. This study thus provides novel insights into carcinogenesis of liver cancer by local interaction between neurotransmitter Ach and hormone receptor AR in HCC. Public Library of Science 2013-04-19 /pmc/articles/PMC3631145/ /pubmed/23620780 http://dx.doi.org/10.1371/journal.pone.0061678 Text en © 2013 Nie et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nie, Huizhen
Cao, Qingzhen
Zhu, Lei
Gong, Yuehua
Gu, Jianren
He, Zuping
Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma
title Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma
title_full Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma
title_fullStr Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma
title_full_unstemmed Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma
title_short Acetylcholine Acts on Androgen Receptor to Promote the Migration and Invasion but Inhibit the Apoptosis of Human Hepatocarcinoma
title_sort acetylcholine acts on androgen receptor to promote the migration and invasion but inhibit the apoptosis of human hepatocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631145/
https://www.ncbi.nlm.nih.gov/pubmed/23620780
http://dx.doi.org/10.1371/journal.pone.0061678
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