Molecular mechanisms of adaptive response of cancer cells to deprivation of both oxygen and nutrient
| Project/Area Number |
17013087
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East |
|---|
Principal Investigator |
ESUMI Hiroyasu National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 東病院、臨床開発センター, 院長 (70160364)
|
|---|
| Project Period (FY) |
2005 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥43,000,000 (Direct Cost: ¥43,000,000)
Fiscal Year 2009: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2008: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2007: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2006: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2005: ¥8,600,000 (Direct Cost: ¥8,600,000)
|
|---|
| Keywords | 低酸素 / 腫瘍血流 / エネルギー代謝 / 栄養欠乏 / ARK5 / 嫌気的解糖 / 嫌気的エネルギー代謝 / AKT / AMPK / グルコース飢餓 / 微小環境 / オートファギー / アミノ酸代謝 / TGF-β / C-MAF / 膵がん |
|---|
| Research Abstract |
Molecular and biochemical mechanisms of adaptive responses of cancer cells to deprivation of both oxygen and nutrient, which mimics tumor microenvironment of hypovascular tumors have been analyzed. In this series of experiments we have found following. 1)Tumor cells especially those from hypovascular tumor show resistance to hypoglycemia and even normal cells can be converted resistant to glucose deprivation by hypoxic condition. 2)AMPK AKT and AMPK-related kinases are involved in the response. 3)These molecules are involved in invasion and metastasis. 4)Under deprivation of nutrient and oxygen, autophagy is involved in cell survival. 5)Anaerobic energy production through fumarate respiration was found to be induced and operated by deprivation of both oxygen and glucose. 6)The metabolomic analysis of human cancer tissues strongly suggested anaerobic energy production through fumarate respiration. The present results opened a way to develop a novel strategy to treat cancer by targeting cancer cells' adaptation to their microenvironment.
|
Report
(6 results)
Research Products
(69 results)
-
-
-
-
[Journal Article] Massive transcriptional start site analysis of human genes in hypoxia cells.2009
Author(s)
Tsuchihara K, Suzuki Y, Wakaguri H, Irie T, Tanimoto K, Hashimoto S, Matsushima K, Mizushima-Sugano J, Yamashita R, Nakai, K, Bentley D, Esumi H, Sugano S.
-
Journal Title
Nucleic Acids Res. 37(7)
Pages: 2249-63
Related Report
-
[Journal Article] Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis Time-of-Flight mass spectrometry.2009
Author(s)
Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M, Esumi H, Soga T.
-
Journal Title
Cancer Res 69(11)
Pages: 4918-25
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] c-Maf expression in angioimmunoblastic T-cell lymphoma.2007
Author(s)
Murakami I Y, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita Y, Morito N, Yoh K, Fujioka Y, Matsuno F, Hata H, Mitsuya H, Imagawa S, Suzuki A, Esumi H, Sakai M, Takahashi S.
-
Journal Title
Am J Surg Pathol 31(11)
Pages: 1695-702
Related Report
-
-
-
-
-
-
-
-
-
-
[Journal Article] Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human.2006
Author(s)
Morito N, Yoh K, Fujioka Y, Nakano T, Shimohata H, Hashimoto Y, Yamada A, Maeda A, Matsuno F, Hata H, Suzuki A, Imagawa S, Mitsuya H, Esumi H, Koyama A, Yamamoto M, Mori N, Takahashi S.
-
Journal Title
Cancer Res 66
Pages: 812-9
Related Report
-
-
-
-
-
-
[Journal Article] Chemopreventive effect of peroxisome proliferators activated receptor gamma on gastric carcinogenesis in mice.2005
Author(s)
Lu J, Imamura K, Nomura S, Mafune K, Nakajima A, Kadowaki T, Kubota N, Terauchi Y, Ishii G., Ochiai A, Esumi H, Kaminishi M.
-
Journal Title
Cancer Res. 65(11)
Pages: 4769-74
Related Report
-
-
[Journal Article] ARK5 is transcriptionally regulated by the Large-MAF Family and mediates IGF-1-induced cell invasion in multiple myeloma; ARK5 is a new molecular determinant of malignant multiple myeloma.2005
Author(s)
Suzuki A, Iida S, Kato-Uranishi M, Tajima E, Zhan F, Hanamura I, Huang Y, Ogura T, Takahashi S, Ueda R, Barlogie B, Shaughnessy J Jr., Esumi H.
-
Journal Title
Oncogene 24
Pages: 6936-44
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
