title: Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress.
abstract: Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are reasonable targets for cancer therapy. However, recent studies have revealed that some non-CSCs/CICs have plastic ability and can dedifferentiate into CSCs/CICs. Therefore, an understanding of the molecular mechanisms that control the plasticity is essential to achieve CSC/CIC-targeting therapy. In this study, we analyzed the plasticity of lung cancer cells and found that lung non-CSCs/CICs can dedifferentiate into CSCs/CICs in accordance with the expression of stem cell transcription factor SOX2. SOX2 expression was induced by the transcription factor HOXA5. Oxidative stress repressed the expression of HDAC8 and then induced histone 3 acetylation and increased the expression of HOXA5 and SOX2. These findings indicate that lung cancer cells have plasticity under a condition of oxidative stress and that HOAX5 has a critical role in dedifferentiation.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saijo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Horibe
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Takaya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Murai
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Kajiwara
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shionoya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Nakatsugawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.|Department of Molecular Therapeutics, Center for Food and Medical Innovation, Hokkaido University, Sapporo, 060-8638, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000107:Acetylation; D000818:Animals; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D058985:Side-Population Cells / Q000378:metabolism*; D014162:Transfection
chemical_list: C489213:HOXA5 protein, human; D006657:Histones; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C409470:HDAC8 protein, human; D006655:Histone Deacetylases
keywords: HOXA5; SOX2; cancer stem cell; lung cancer; plasticity