title: Snail modulates cell metabolism in MDCK cells.
abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of key enzymes. This results in enhanced glucose dependency and leads to cell death under low-glucose conditions. On the other hand, the reduced requirements for oxygen and nutrients from the surrounding environment, might confer the resistance to cell death induced by hypoxia and malnutrition.
authors: Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan. haraguci@m3.kufm.kagoshima-u.ac.jp
authors: Misako
authors: M
authors: Haraguchi
authors: Hiroko P
authors: HP
authors: Indo
authors: Yasumasa
authors: Y
authors: Iwasaki
authors: Yoichiro
authors: Y
authors: Iwashita
authors: Tomoko
authors: T
authors: Fukushige
authors: Hideyuki J
authors: HJ
authors: Majima
authors: Kimiko
authors: K
authors: Izumo
authors: Masahisa
authors: M
authors: Horiuchi
authors: Takuro
authors: T
authors: Kanekura
authors: Tatsuhiko
authors: T
authors: Furukawa
authors: Masayuki
authors: M
authors: Ozawa
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D010101:Oxygen Consumption / Q000235:genetics; D000071250:Snail Family Transcription Factors; D013385:Succinate Dehydrogenase; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D007521:Isocitrate Dehydrogenase; D013385:Succinate Dehydrogenase; D000154:Aconitate Hydratase; D005947:Glucose