title: All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.
abstract: Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expressions of RA-biosynthesis-related dehydrogenases were highly expressed in hepatocellular carcinoma. All-trans retinoic acid (ATRA) differentiated hCSCs through inhibiting the function of β-catenin in vitro. ATRA also inhibited the function of PI3K-AKT and enhanced GSK-3β-dependent degradation of phosphorylated β-catenin. Furthermore, ATRA and β-catenin silencing both increased hCSC sensitivity to docetaxel treatment. Our results suggest that targeting β-catenin will provide extra benefits for ATRA-mediated treatment of hepatic cancer patients.
authors.affiliation: Affiliated Calmette Hospital of Kunming Medical University, Kunming, Yunnan Province, 650011, P. R. China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan Province, 650091, P. R. China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Wang
authors.affiliation: Affiliated Calmette Hospital of Kunming Medical University, Kunming, Yunnan Province, 650011, P. R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Affiliated Calmette Hospital of Kunming Medical University, Kunming, Yunnan Province, 650011, P. R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Bai
authors.affiliation: Affiliated Calmette Hospital of Kunming Medical University, Kunming, Yunnan Province, 650011, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Affiliated Calmette Hospital of Kunming Medical University, Kunming, Yunnan Province, 650011, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, Yunnan Province, 650091, P. R. China.
authors.forename: Meizhang
authors.initials: M
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D006023:Glycoproteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D034741:RNA, Small Interfering; D043823:Taxoids; D051176:beta Catenin; D000077143:Docetaxel; D014212:Tretinoin; D010088:Oxidoreductases