title: Implication of snail in metabolic stress-induced necrosis.
abstract: BACKGROUND
  Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD) resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.
  
  
  RESULTS
  Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS)-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh) RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.
  
  
  CONCLUSIONS
  Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan, Korea.
authors: Cho Hee
authors: CH
authors: Kim
authors: Hyun Min
authors: HM
authors: Jeon
authors: Su Yeon
authors: SY
authors: Lee
authors: Min Kyung
authors: MK
authors: Ju
authors: Ji Young
authors: JY
authors: Moon
authors: Hye Gyeong
authors: HG
authors: Park
authors: Mi-Ae
authors: MA
authors: Yoo
authors: Byung Tae
authors: BT
authors: Choi
authors: Jong In
authors: JI
authors: Yook
authors: Sung-Chul
authors: SC
authors: Lim
authors: Song Iy
authors: SI
authors: Han
authors: Ho Sung
authors: HS
authors: Kang
mesh_terms: D015687:Cell Hypoxia; D005947:Glucose / Q000172:deficiency; D006801:Humans; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D005947:Glucose