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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0182149
JournalPLoS One
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

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protein phosphorylation
lung neoplasms
Epidermal Growth Factor Receptor
Lung Neoplasms
Cells
neoplasms
Neoplasms
Tumors
epidermal growth factor receptors
neoplasm cells
Recurrence
Neoplastic Stem Cells
Stem cells
cell viability
stem cells
Cell Survival
cells
drugs
mutants

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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.

In: PLoS One, Vol. 12, No. 8, e0182149, 01.08.2017.

Research output: Contribution to journalArticle

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. / YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells. In: PLoS One. 2017 ; Vol. 12, No. 8.
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