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Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress

2016; Impact Journals LLC; Volume: 7; Issue: 31 Linguagem: Inglês

10.18632/oncotarget.10571

1949-2553

Hiroshi Saijo, Yoshihiko Hirohashi, Toshihiko Torigoe, Ryota Horibe, Akari Takaya, Aiko Murai, Terufumi Kubo, Toshimitsu Kajiwara, Tsutomu Tanaka, Yosuke Shionoya, Eri Yamamoto, Reo Maruyama, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Yasuaki Tamura, Yasushi Sasaki, Takashi Tokino, Hiromu Suzuki, Tôru Kondo, Hiroki Takahashi, Noriyuki Sato,

PI3K/AKT/mTOR signaling in cancer

// Hiroshi Saijo 1, 2 , Yoshihiko Hirohashi 1 , Toshihiko Torigoe 1 , Ryota Horibe 1, 2 , Akari Takaya 1 , Aiko Murai 1 , Terufumi Kubo 1 , Toshimitsu Kajiwara 1 , Tsutomu Tanaka 1 , Yosuke Shionoya 1, 2 , Eri Yamamoto 1 , Reo Maruyama 3 , Munehide Nakatsugawa 1 , Takayuki Kanaseki 1 , Tomohide Tsukahara 1 , Yasuaki Tamura 1, 4 , Yasushi Sasaki 5 , Takashi Tokino 5 , Hiromu Suzuki 3 , Toru Kondo 6 , Hiroki Takahashi 2 , Noriyuki Sato 1 1 Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan 2 Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan 3 Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan 4 Department of Molecular Therapeutics, Center for Food and Medical Innovation, Hokkaido University, Sapporo, 060-8638, Japan 5 Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan 6 Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-8638, Japan Correspondence to: Yoshihiko Hirohashi, email: hirohash@sapmed.ac.jp Toshihiko Torigoe, email: torigoe@sapmed.ac.jp Keywords: cancer stem cell, plasticity, lung cancer, SOX2, HOXA5 Received: August 26, 2015 Accepted: June 26, 2016 Published: July 13, 2016 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.