title: Aldehyde dehydrogenase 1A1 up-regulates stem cell markers in benzo[a]pyrene-induced malignant transformation of BEAS-2B cells.
abstract: Recently, Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed to be a common marker of cancer stem cells and can be induced by benzo[a]pyrene (B[a]P) exposure. However, the underlying mechanism of how ALDH1A1 contributes to B[a]P-induced carcinogenesis in human bronchial epithelial cells remains unclear. Here, we found that B[a]P up-regulated expression levels of stem cell markers (ABCG2, SOX2, c-Myc and Klf4), epithelial-mesenchymal transition (EMT) associated genes (SNAIL1, ZEB1, TWIST and β-CATENIN) and cancer-related long non-coding RNAs (lncRNAs; HOTAIR and MALAT-1) in malignant B[a]P-transformed human bronchial epithelial cells (BEAS-2B-T cells), and these up-regulations were dependent on increased expression of ALDH1A1. The inhibition of endogenous ALDH1A1 expression down-regulated expression levels of stem cell markers and reversed the malignant phenotype as well as reduced the chemoresistance of BEAS-2B-T cells. In contrast, the overexpression of ALDH1A1 in BEAS-2B cells increased the expression of stem cell markers, facilitated cell transformation, promoted migratory ability and enhanced the drug resistance of BEAS-2B cells. Overall, our data indicates that ALDH1A1 promotes a stemness phenotype and plays a critical role in the BEAS-2B cell malignant transformation induced by B[a]P.
authors.affiliation: Department of Medical Genetics & Cell Biology, Guangzhou Medical University, Guangzhou 511400, PR China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Genetics & Cell Biology, Guangzhou Medical University, Guangzhou 511400, PR China.
authors.forename: Ruitao
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of pathology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
authors.forename: Junlian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Center of Medical Functional Experiments, Guangzhou Medical University, Guangzhou 511400, PR China.
authors.forename: Yanxuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathogenic Biology, Guangzhou Medical University, Guangzhou 511400, PR China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics & Cell Biology, Guangzhou Medical University, Guangzhou 511400, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Second Hospital of Jilin University, Changchun 130041, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Biological Experiment Center, the Second People's Hospital of Guangdong Province, Guangzhou 510317, PR China. Electronic address: hwf982353@163.com.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Medical Genetics & Cell Biology, Guangzhou Medical University, Guangzhou 511400, PR China. Electronic address: zjcyx@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D001564:Benzo(a)pyrene / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D050697:Retinal Dehydrogenase; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004785:Environmental Pollutants; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D001564:Benzo(a)pyrene; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: Aldehyde dehydrogenase 1A1; Benzo[a]pyrene; Malignant transformation; Stem cell markers