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TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis.

Yuzhen WangYingchun WangWen LiuLu DingXiaodi ZhangBo WangZheng TongXuetian YueChunyang LiLiyun XuZhuanchang WuXiaohong LiangChunhong MaLifen Gao
Published in: Cell death & disease (2023)
Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin and mucin domain-containing molecule 4 (TIM-4) promotes the development and progression of lung cancer. However, the role of TIM-4 in mitochondria homeostasis in tumor cells remains completely unknown. In this study, we found that TIM-4 promoted growth and proliferation of lung cancer cells by the oxidative phosphorylation (OXPHOS) pathway. Consistently, inhibition of OXPHOS reversed TIM-4-induced proliferation of lung cancer cells. Notably, TIM-4 promoted mitochondrial fusion via enhancing L-OPA1 protein expression. Mechanistically, TIM-4 regulated protein of L-OPA1 through the PI3K/AKT pathway, and TIM-4 interacted with ANXA2 to promote the activation of PI3K/AKT signaling. Collectively, TIM-4 promotes oxidative phosphorylation of lung cancer cells to accelerate tumor progress via ANXA2/PI3K/AKT/OPA1 axis, which sheds significant new lights on the potential role of TIM-4 in regulating tumor cell metabolism.
Keyphrases
  • pi k akt
  • signaling pathway
  • cell cycle arrest
  • cell proliferation
  • cell death
  • risk assessment
  • protein kinase
  • endothelial cells