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

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...

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Published in:Oncotarget 2016-08, Vol.7 (31), p.50043-50056
Main Authors: Saijo, Hiroshi, Hirohashi, Yoshihiko, Torigoe, Toshihiko, Horibe, Ryota, Takaya, Akari, Murai, Aiko, Kubo, Terufumi, Kajiwara, Toshimitsu, Tanaka, Tsutomu, Shionoya, Yosuke, Yamamoto, Eri, Maruyama, Reo, Nakatsugawa, Munehide, Kanaseki, Takayuki, Tsukahara, Tomohide, Tamura, Yasuaki, Sasaki, Yasushi, Tokino, Takashi, Suzuki, Hiromu, Kondo, Toru, Takahashi, Hiroki, Sato, Noriyuki
Format: Article
Language:English
Subjects:
Acetylation
Animals
Cell Dedifferentiation
Cell Proliferation
Gene Expression Regulation, Neoplastic
Histone Deacetylases - metabolism
Histones - chemistry
Homeodomain Proteins - metabolism
Humans
Lung Neoplasms - metabolism
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Transplantation
Neoplastic Stem Cells - metabolism
Oxidative Stress
Repressor Proteins - metabolism
Research Paper
RNA, Small Interfering - metabolism
Side-Population Cells - metabolism
SOXB1 Transcription Factors - metabolism
Transfection
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.10571