Role of TNF-TAK1 signaling pathway in tumor microenvironments of metastasis
| Project/Area Number |
23590071
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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 |
Biological pharmacy
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| Research Institution | University of Toyama |
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Principal Investigator |
SAKURAI Hiroaki 富山大学, 大学院医学薬学研究部(薬学), 教授 (00345571)
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| Co-Investigator(Renkei-kenkyūsha) |
SAIKI Ikuo 富山大学, 和漢医薬学総合研究所, 教授 (80133776)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | チロシンキナーゼ型受容体 / TNF / TAK1 / EphA2 / RSK / Helicobacter pylori / EGFR / 肺がん / チロシンキナーゼ / リン酸化 / がん / 炎症 / シグナル伝達 / MAPK / がん転移 / がん微小環境 / TNF-α |
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| Outline of Final Research Achievements |
Crosstalk between inflammatory signaling pathways and receptor tyrosine kinases has been revealed as an indicator of cancer malignant progression. In the present study, we focus on EphA2 receptor tyrosine kinase. It has been reported that ligand-independent phosphorylation of EphA2 at Ser-897 is induced by Akt. We show that inflammatory cytokines promote RSK-, not Akt-, dependent phosphorylation of EphA2 at Ser-897. The RSK-EphA2 signaling pathway controls cell migration and invasion of metastatic breast cancer cells. Moreover, Ser-897-phosphorylated EphA2 co-localizes with phosphorylated active form of RSK in various human tumor specimens, and this double positivity is related to poor survival in lung cancer patients, especially those with a smoking history. These results indicate that the phosphorylation of EphA2 at Ser-897 is controlled by RSK and the RSK-EphA2 axis might contribute to cell motility and promote tumor malignant progression.
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Role of tyrosine kinase-independent phosphorylation of EGFR with activating mutation in cisplatin-treated lung cancer cells.2015
Author(s)
Refaat A., Aminullah, Zhou Y., Kawanishi M., Tomaru R., Abdelhamed S., Shin M.S., Koizumi K., Yokoyama S., Saiki I., and Sakurai H.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 458
Issue: 4
Pages: 856-861
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Inverse correlation between Thr-669 and constitutive tyrosine phosphorylation in the asymmetric epidermal growth factor receptor dimer conformation.2013
Author(s)
Sato K., Shin M.S., Sakimura A., Zhou Y., Tanaka T., Kawanishi M., Kawasaki Y., Yokoyama S., Koizumi K., Saiki I., and Sakurai H.
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Journal Title
Cancer Science
Volume: 104
Issue: 10
Pages: 1315-1322
DOI
Related Report
Peer Reviewed
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