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Implication of snail in metabolic stress-induced necrosis.

 Cho Hee Kim  ;  Hyun Min Jeon  ;  Su Yeon Lee  ;  Min Kyung Ju  ;  Ji Young Moon  ;  Hye Gyeong Park  ;  Mi-Ae Yoo  ;  Byung Tae Choi  ;  Jong In Yook  ;  Sung-Chul Lim  ;  Song Iy Han  ;  Ho Sung Kang 
 PLOS ONE, Vol.6(3) : e18000, 2011 
Journal Title
Issue Date
Cell Hypoxia ; Glucose/deficiency ; Humans ; Immunohistochemistry ; Membrane Potential, Mitochondrial ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Mitochondrial Membrane Transport Proteins/metabolism ; Necrosis/metabolism* ; Necrosis/pathology* ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; Snail Family Transcription Factors ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology ; Stress, Physiological* ; Transcription Factors/metabolism* ; Tumor Cells, Cultured
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.

METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.
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2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
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