title: Acetylcholine acts on androgen receptor to promote the migration and invasion but inhibit the apoptosis of human hepatocarcinoma.
abstract: 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.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Nie
authors.forename: Qingzhen
authors.initials: Q
authors.lastname: Cao
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Gong
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.forename: Zuping
authors.initials: Z
authors.lastname: He
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D015741:Metribolone / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014105:Tosyl Compounds / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D011950:Receptors, Cholinergic; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014105:Tosyl Compounds; D015741:Metribolone; D008464:Mecamylamine; C053541:bicalutamide; D051057:Proto-Oncogene Proteins c-akt; D000109:Acetylcholine