Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by activating the unfolded protein response

Hsin Yi Chang, Hsuan Cheng Huang, Tsui Chin Huang, Pan Chyr Yang, Yi Ching Wang, Hsueh Fen Juan

研究成果: 雜誌貢獻文章

39 引文 (Scopus)

摘要

Ectopic expression of the mitochondrial F1F0-ATP synthase on the plasma membrane has been reported to occur in cancer, but whether it exerts a functional role in this setting remains unclear. Here we show that ectopic ATP synthase and the electron transfer chain exist on the plasma membrane in a punctuated distribution of lung adenocarcinoma cells, where it is critical to support cancer cell proliferation. Applying ATP synthase inhibitor citreoviridin induced cell cycle arrest and inhibited proliferation and anchorage-independent growth of lung cancer cells. Analysis of protein expression profiles after citreoviridin treatment suggested this compound induced the unfolded protein response (UPR) associated with phosphorylation the translation initiation factor 2α (eIF2α), triggering cell growth inhibition. Citreoviridin-enhanced eIF2α phosphorylation could be reversed by siRNA-mediated attenuation of the UPR kinase PKR-like endoplasmic reticulum kinase (PERK) combined with treatment with the antioxidant N-acetylcysteine, establishing that reactive oxygen species (ROS) boost UPR after citreoviridin treatment. Thus, a coordinate elevation of UPR and ROS initiates a positive feedback loop that convergently blocks cell proliferation. Our findings define a molecular function for ectopic ATP synthase at the plasma membrane in lung cancer cells and they prompt further study of its inhibition as a potential therapeutic approach.
原文英語
頁(從 - 到)4696-4706
頁數11
期刊Cancer Research
72
發行號18
DOIs
出版狀態已發佈 - 九月 15 2012

指紋

Unfolded Protein Response
Adenosine Triphosphate
Cell Membrane
Growth
Reactive Oxygen Species
Lung Neoplasms
Prokaryotic Initiation Factor-2
Mitochondrial Proton-Translocating ATPases
Phosphorylation
Cell Proliferation
eIF-2 Kinase
Acetylcysteine
Cell Cycle Checkpoints
Endoplasmic Reticulum
Small Interfering RNA
Neoplasms
Phosphotransferases
Antioxidants
Electrons
Adenocarcinoma of lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by activating the unfolded protein response. / Chang, Hsin Yi; Huang, Hsuan Cheng; Huang, Tsui Chin; Yang, Pan Chyr; Wang, Yi Ching; Juan, Hsueh Fen.

於: Cancer Research, 卷 72, 編號 18, 15.09.2012, p. 4696-4706.

研究成果: 雜誌貢獻文章

Chang, Hsin Yi ; Huang, Hsuan Cheng ; Huang, Tsui Chin ; Yang, Pan Chyr ; Wang, Yi Ching ; Juan, Hsueh Fen. / Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by activating the unfolded protein response. 於: Cancer Research. 2012 ; 卷 72, 編號 18. 頁 4696-4706.
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