Impaired mitophagy activates mtROS/HIF-1α interplay and increases cancer aggressiveness in gastric cancer cells under hypoxia

International Journal of Oncology
Masaaki ShidaHirokazu Noshiro

Abstract

Mitochondrial autophagy (mitophagy) is a selective form of autophagy and a critical step in excluding mitochondria damaged by stress, including hypoxia. This study aimed to determine whether the integrity of mitophagy affected production of the mitochondrial reactive oxygen species (mtROS), hypoxia inducible factor (HIF)-1α expression and aggressive characteristics in GC cells under hypoxia. Three GC cell lines, 44As3, 58As9 and MKN45, were investigated in this study. HIF-1α expression was induced in the three GC cell lines under hypoxia, with higher expression observed in 44As3 and 58As9 cells compared with MKN45 cells. Cell survival and invasion abilities under hypoxia were significantly stronger in 44As3 and 58As9 cells than MKN45 cells. Moreover, mtROS accumulated in a time-dependent manner in 44As3 and 58As9 cells, but not in MKN45 cells. ROS scavenger N-acetyl-L-cysteine (NAC) treatment resulted in strong attenuation of HIF-1α expression, whereas HIF-1α knockdown increased ROS production in the three GC cell lines under hypoxia. These results suggested that the mtROS/HIF-1α interplay affected the hypoxia-induced cancer aggressiveness. Assessment of mitophagy by LC3-I/II conversion, SQSTM1/p62 degradation and specific fluo...Continue Reading

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Jan 13, 2018·Molecular Medicine Reports·Huiying QiaoRong Lv
Sep 16, 2020·Journal of Experimental & Clinical Cancer Research : CR·Mingyao HuangHangyu Li
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Sep 4, 2021·Mitochondrion·Ashutosh TripathiAnilkumar Pillai

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