title: Inhibition of Hedgehog signaling pathway impedes cancer cell proliferation by promotion of autophagy.
abstract: Multiple lines of evidence implicate that aberrant activation of Hedgehog (Hh) signaling is involved in a variety of human cancers. However, the molecular mechanisms underlying how cancer cells respond to Hh inhibition remain to be elucidated. In this study, we found that blockade of Hh signaling suppresses cell proliferation in human cancer cells. Microarray analysis revealed that differentially expressed genes (DEGs) in human cancer cells are enriched in autophagy pathway in response to the inhibition of Hh signaling. Interestingly, inhibition of Hh signaling induced autophagy, whereas activation of Hh signaling by ligand treatments prevented the induction of autophagy. In addition, inhibition of autophagy by 3-methyladenine (3-MA) partially suppressed cytotoxicity induced by inhibition of Hh signaling. Finally, in autophagy deficient cells, cytotoxic effect triggered by inhibition of Hh signaling was partially reversed, indicating the modulation of autophagy by Hh signaling is autophagy-specific. These results suggest that inhibition of Hh signaling impedes cancer cell proliferation in part through induction of autophagy.
authors.affiliation: Department of Biochemistry, School of Medicine, Nanchang University, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Biochemistry, School of Medicine, Nanchang University, China; Institute of Translational Medicine, Nanchang University, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Deng
authors.affiliation: The Second Affiliated Hospital of Nanchang University, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Nanchang University, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Nanchang University, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Nanchang University, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.affiliation: The First Affiliated Hospital of Nanchang University, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shao
authors.affiliation: The First Affiliated Hospital of Nanchang University, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Nanchang University, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Rao
authors.affiliation: The First Affiliated Hospital of Nanchang University, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Epidemiology & Biostatistics, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: quqinlu@ncu.edu.cn.
authors.forename: Quqin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects; D000075746:Zinc Finger Protein Gli2
chemical_list: C551027:GANT 61; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011725:Pyridines; D011743:Pyrimidines; D000075746:Zinc Finger Protein Gli2; C025946:3-methyladenine; D000225:Adenine
keywords: Autophagy; Cell proliferation; Hedgehog signaling; SQSTM1/p62; Transcription factor Gli