A novel mechanism increasing gastric cancer aggressiveness via impaired mitophagy
| Project/Area Number |
15K10103
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Saga University |
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Principal Investigator |
Nakamura Jun 佐賀大学, 医学部, 客員研究員 (60404175)
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| Co-Investigator(Kenkyū-buntansha) |
北島 吉彦 佐賀大学, 医学部, 客員研究員 (30234256)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | マイトファジー / HIF-1α / ROS / 胃癌 / 低酸素 |
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| Outline of Final Research Achievements |
The hypoxic environment is substantial in solid tumors including gastric cancer (GC), where it accelerates their malignant behavior via HIF-1α pathway. Whereas, hypoxia is known to stimulate ROS production from mitochondrial complex III in the electron transport chain, and mitochondrial ROS (mtROS) stabilize HIF-1α leads to increased cancer aggressiveness.
Mitochondrial autophagy (mitophagy) is a selective form of autophagy and a critical step in excluding mitochondria damaged by stress, including hypoxia. Our data suggested that mtROS is accumulated under hypoxia in scirrhous GC cells due to impaired mitophagy, while mtROS is controlled at a low level through the normal mitophagy process in non-scirrhous GC cells.
This study demonstrated that the integrity of mitophagy determined the cancer aggressiveness of GC cells under hypoxic environment via the activation of the mtROS/HIF-1α interplay.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Hypoxia-induced ANGPTL4 sustains tumour growth and anoikis resistance through different mechanisms in scirrhous gastric cancer cell lines.2017
Author(s)
Baba K, Kitajima Y, Miyake S, Nakamura J, Wakiyama K, Sato H, Okuyama K, Kitagawa H, Tanaka T, Hiraki M, Yanagihara K, Noshiro H.
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 11127-11127
DOI
Related Report
Peer Reviewed / Open Access
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