慢性的エネルギー飢餓環境におけるDNA脱メチル化経路を介したがん転移機構の解明
Publicly Offered Research
Project Area | Crosstalk of transcriptional control and energy pathways by hub metabolites |
Project/Area Number |
26116722
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Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Kumamoto University |
Principal Investigator |
尾池 雄一 熊本大学, 大学院生命科学研究部 (医), 教授 (90312321)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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Keywords | がん微小環境 / 転移 / エピゲノム / DNA脱メチル化 / ヒストン修飾 |
Outline of Annual Research Achievements |
がん原発巣におけるがん細胞のエピゲノム変化と転移との関連解明実験において、腫瘍微小環境においてがん細胞で発現誘導されるDNA脱メチル化酵素が、解糖系関連酵素遺伝子の発現誘導に関与していることを見出した。現在、DNA脱メチル化酵素をノックダウンしたがん細胞株を用いた移植実験を実施しており、がん原発巣における低酸素環境がDNA脱メチル化酵素を介したエピゲノム変化やこれに伴う細胞代謝の変化を引き起こし、がん細胞の増殖や生存に寄与している可能性を検討している。移植前のがん細胞と移植後に肺転移したがん細胞間で細胞代謝を比較したところ、肺転移したがん細胞では、解糖系が亢進していることを見出した。さらに、移植前のがん細胞に比べ移植後に肺転移したがん細胞では解糖系関連酵素遺伝子の発現が亢進していることが明らかとなった。そこで、肺転移したがん細胞における解糖系関連酵素遺伝子の発現亢進のメカニズムを検討したところ、肺転移した骨肉腫細胞ではMEK-ERK-HIF経路が活性化し、細胞代謝が解糖系にシフトしていることが明らかとなった。また、移植前のがん細胞と移植後に肺転移したがん細胞をそれぞれ経静脈的にマウスに投与し、肺におけるがん細胞の増殖を検討すると、移植前のがん細胞ではほとんど増殖が認められないのに対し、肺転移したがん細胞では肺組織における増殖が認められた。以上より、原発巣におけるがん細胞のエピゲノム変化とこれに伴う細胞代謝変化が転移したがん細胞においても記憶として維持され、その増殖や生存に寄与している可能性が示唆された。
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Research Progress Status |
27年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
27年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(56 results)
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[Journal Article] Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.2016
Author(s)
Jun Morinaga, Tsuyoshi Kadomatsu, Keishi Miyata, Motoyoshi Endo, Kazutoyo Terada, Zhe Tian, Taichi Sugizaki, Hiroki Tanigawa, Jiabin Zhao, Shunshun Zhu, Michio Sato, Kimi Araki, Ken-ichi Iyama, Kengo Tomita, Masashi Mukoyama, Kimio Tomita, Kenichiro Kitamura, Yuichi Oike
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Journal Title
Kidney International
Volume: 89
Issue: 2
Pages: 327-341
DOI
Related Report
Peer Reviewed
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[Journal Article] Persistent activation of cGMP-dependent protein kinase by a nitrated cyclic nucleotide via site specific protein S-guanylation2016
Author(s)
Akashi S, Ahmed KA, Sawa T, Ono K, Tsutsuki H, Burgoyne JR, Ida T, Horio E, Prysyazhna O, Oike Y, Rahaman MM, Eaton P, Fujii S, Akaike T.
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Journal Title
Biochemistry
Volume: 55
Issue: 5
Pages: 751-761
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The exacerbating roles of CCAAT/enhancer-binding protein homologous protein (CHOP) in the development of bleomycin-induced pulmonary fibrosis and the preventive effects of tauroursodeoxycholic acid (TUDCA) against pulmonary fibrosis in mice.2015
Author(s)
Tanaka Y, Ishitsuka Y, Hayasaka M, Yamada Y, Miyata K, Endo M, Kondo Y, Moriuchi H, Irikura M, Tanaka K, Mizushima T, Oike Y, Irie T.
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Journal Title
Pharmacol Res.
Volume: 99
Pages: 52-62
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.2015
Author(s)
Masuda T, Endo M, Yamamoto Y, Odagiri H, Kadomatsu T, Nakamura T, Tanoue H, Ito H, Yugami M, Miyata K, Morinaga J, Horiguchi H, Motokawa I, Terada K, Morioka MS, Manabe I, Iwase H, Mizuta H, Oike Y.
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Journal Title
Sci Rep.
Volume: 5
Issue: 1
Pages: 9170-9170
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Muscle-liver-fat signaling axis is essential for central control of adaptive adipose remodeling2015
Author(s)
Shimizu N, Maruyama T, Yoshikawa N, Matsumiya R, Ma Y, Ito N, Tasaka Y, Kuribara-Souta A, Miyata K, Oike Y, Berger S, Schutz G, Takeda S & Tanaka H
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Journal Title
Nat Commun
Volume: -
Issue: 1
Pages: 6693-6693
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans.2015
Author(s)
Wei FY, Zhou B, Suzuki T, Miyata K, Ujihara Y, Horiguchi H, Takahashi N, Xie P, Michiue H, Fujimura A, Kaitsuka T, Matsui H, Koga Y, Mohri S, Suzuki T, Oike Y, Tomizawa K.
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Journal Title
Cell Metab
Volume: 21
Issue: 3
Pages: 413-6
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.2014
Author(s)
Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y.
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Journal Title
Cancer Science
Volume: 105
Issue: 12
Pages: 1550-1559
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.2014
Author(s)
Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, Miki Y, Yamamoto K, Nishito Y, Kobayashi T, Ikeda K, Taguchi R, Hara S, Ida S, Miyamoto Y, Watanabe M, Baba H, Miyata K, Oike Y, Gelb MH, Murakami M.
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Journal Title
Cell Metab.
Volume: 20
Issue: 1
Pages: 119-132
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Tissue Inhibitor of Metalloproteinase-3 Knockout Mice Exhibit Enhanced Energy Expenditure through Thermogenesis2014
Author(s)
Hanaoka Y, Yasuda O, Soejima H, Miyata K, Yamamoto E, Izumiya Y, Maeda N, Ohishi M, Rakugi H, Oike Y, Kim-Mitsuyama S, Ogawa H
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Journal Title
PLoS One
Volume: 9
Issue: 4
Pages: e94930-e94930
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] SIRT7 controls hepatic lipid metabolism by regulating the ubiquitin-proteasome pathway.2014
Author(s)
Yoshizawa T, Karim Md. F, Sato Y, Senokuchi T, Miyata K, Fukuda T, Go C, Tasaki M, Uchimura K, Kadomatsu T, Tian Z, Smolka C, Sawa T, Kakeya M, Tomizawa K, Ando Y, Araki E, Akaike T, Braun T, Oike Y, Bober E, Yamagata K.
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Journal Title
Cell Metab.
Volume: 9
Issue: 4
Pages: 712-721
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum ANGPTL2 levels reflect clinical features of breast cancer patients: implications for the pathogenesis of breast cancer metastasis.2014
Author(s)
Endo M, Yamamoto Y, Nakano M, Masuda T, Odagiri H, Horiguchi H, Miyata K, Kadomatsu T, Motokawa I, Okada S, Iwase H, Oike Y.
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Journal Title
The International Journal of Biological Markers
Volume: 印刷中
Issue: 3
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access
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