| Project/Area Number |
26713042
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
BABA Yoshifumi 熊本大学, 大学院生命科学研究部(医), 講師 (20599708)
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| Research Collaborator |
KOSUMI Keisuke 熊本大学, 医学部附属病院, 非常勤診療医師 (50594884)
HARADA Kazuto 熊本大学, 医学部附属病院, 非常勤診療医師 (70608869)
KITANO Yuki 熊本大学, 大学院医学教育部, 大学院生
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2014: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Keywords | がん代謝 / エピジェネティクス / 食道癌 / バイオマーカー / Cancer metabolism / epigenetics / esophageal cancer / LSD1 / LINE-1 / 細胞外フラックスアナライザー / NRF2 / epigenomic biomarker |
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| Outline of Final Research Achievements |
First, for revealing the role of LSD1 in cancer metabolism, we evaluated two major energy pathways by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) with an extracellular flux analyzer. LSD1 knockdown significantly suppressed the invasive activity and glucose uptake of cancerous cells, reduced their ECAR and increased their OCR and OCR/ECAR (Int J Cancer 2016). Second, we focused on Nrf2 which is a master transcription regulator of stress responses. We found that metabolic reprogramming to glutathione metabolism, and ROS detoxification by activation of Nrf2, enhanced cancer progression and led to poor clinical outcome in esophageal cancer patients. The identification of new prognostic or predictive markers for esophageal cancer could improve the use of risk-adapted treatment strategies and help to stratify patients for drugs targeting these tumor characteristics in future clinical trials (Cancer Lett 2016).
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