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YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells

Cheng, Chun-Chia ; Chang, Jungshan ; Huang, Stanley Ching-Cheng ; Lin, Huan-Chau ; Ho, Ai-Sheng ; Lim, Ken-Hong ; Chang, Chun-Chao ; Huang, Ling ; Chang, Yu-Cheng ; Chang, Yi-Fang ; Wu, Cheng-Wen Lee, Jung Weon

PloS one, 2017-08, Vol.12 (8), p.e0182149 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells
Autor: Cheng, Chun-Chia ; Chang, Jungshan ; Huang, Stanley Ching-Cheng ; Lin, Huan-Chau ; Ho, Ai-Sheng ; Lim, Ken-Hong ; Chang, Chun-Chao ; Huang, Ling ; Chang, Yu-Cheng ; Chang, Yi-Fang ; Wu, Cheng-Wen
Lee, Jung Weon
Assuntos: Analysis ; Antineoplastic Agents - pharmacology ; Apoptosis ; Biology and Life Sciences ; Cancer ; Cell Line, Tumor ; Cell survival ; Clinical medicine ; Drug Evaluation, Preclinical ; Drug resistance ; Drug therapy ; Epidermal growth factor ; Epidermal growth factor receptors ; Epidermal growth factors ; Epigenetics ; Gastroenterology ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - physiology ; Hematology ; Hepatology ; Histocompatibility Antigens - metabolism ; Histone-Lysine N-Methyltransferase - antagonists & inhibitors ; Histone-Lysine N-Methyltransferase - metabolism ; Humans ; Imidazoles - pharmacology ; Inhibition ; Internal medicine ; Ionizing radiation ; Kinases ; Lung cancer ; Lung diseases ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Medical prognosis ; Medical research ; Medicine ; Medicine and Health Sciences ; Methylation - drug effects ; Mutation ; Naphthoquinones - pharmacology ; Oct-4 protein ; Octamer Transcription Factor-3 - metabolism ; Oncology ; Phosphorylation ; Phosphorylation - drug effects ; Phosphorylation - physiology ; Physical Sciences ; Proteins ; Quinazolines - pharmacology ; Receptor, Epidermal Growth Factor - genetics ; Receptor, Epidermal Growth Factor - metabolism ; Research and Analysis Methods ; Risk factors ; RNA, Messenger - metabolism ; Stem cells
É parte de: PloS one, 2017-08, Vol.12 (8), p.e0182149
Notas: Competing Interests: The authors have declared that no competing interests exist.
Descrição: Cancer stem cell survival is the leading factor for tumor recurrence after tumor-suppressive treatments. Therefore, specific and efficient inhibitors of cancer stemness must be discovered for reducing tumor recurrence. YM155 has been indicated to significantly reduce stemness-derived tumorsphere formation. However, the pharmaceutical mechanism of YM155 against cancer stemness is unclear. This study investigated the potential mechanism of YM155 against cancer stemness in lung cancer. Tumorspheres derived from epidermal growth factor receptor (EGFR)-mutant HCC827 and EGFR wild-type A549 cells expressing higher cancer stemness markers (CD133, Oct4, and Nanog) were used as cancer stemness models. We observed that EGFR autophosphorylation (Y1068) was higher in HCC827- and A549-derived tumorspheres than in parental cells; this autophosphorylation induced tumorsphere formation by activating G9a-mediated stemness. Notably, YM155 inhibited tumorsphere formation by blocking the autophosphorylation of EGFR and the EGFR-G9a-mediated stemness pathway. The chemical and genetic inhibition of EGFR and G9a revealed the significant role of the EGFR-G9a pathway in maintaining the cancer stemness property. In conclusion, this study not only revealed that EGFR could trigger tumorsphere formation by elevating G9a-mediated stemness but also demonstrated that YM155 could inhibit this formation by simultaneously blocking EGFR autophosphorylation and G9a activity, thus acting as a potent agent against lung cancer stemness.
Editor: United States: Public Library of Science
Idioma: Inglês

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YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells

Cheng, Chun-Chia ; Chang, Jungshan ; Huang, Stanley Ching-Cheng ; Lin, Huan-Chau ; Ho, Ai-Sheng ; Lim, Ken-Hong ; Chang, Chun-Chao ; Huang, Ling ; Chang, Yu-Cheng ; Chang, Yi-Fang ; Wu, Cheng-Wen Lee, Jung Weon

United States: Public Library of Science

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