| Project/Area Number |
16K08706
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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 |
Experimental pathology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 扁平上皮がん / THG-1 / 分子標的治療 / タンパク質相互作用 / ペプチド / THG-1 / TSC22D4 / THG-1 ノックアウトマウス / TSC22D4 / EGF / Ras / THF-1 |
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| Outline of Final Research Achievements |
Carcinoma cells exhibit a high level of robustness against environmental stresses, metabolic disorders and therapeutic efforts. Here, we provide a novel mechanism of the squamous cell carcinoma development by THG-1, a Tsc-22 family protein. THG-1(TSC22D4), a member of TSC-22 family, is expressed in the basal layer of normal squamous epithelium and overexpressed in squamous cell carcinomas. THG-1 is phosphorylated by Ras-ERK pathway, which promotes cell proliferation, invasion and tumorigenesis. However, molecular functions and physiological roles of THG-1 have not been clear. Therefore, we identified the THG-interacting proteins using proteomic approach. THG-1 interacts with several factors that regulate the cell proliferation, cytoprotection, metabolism and microenvironment. Our resutls highlight the pivotal roles of THG-1 as a novel regulator of tumorigenssis under the oncogenic signaling pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
扁平上皮がんの治療は、外科手術、放射線、化学療法であるが、転移を伴う進行がんの予後を劇的に改善できる分子標的治療薬は未だ開発されていない。本研究により申請者はTHG-1と呼ばれる分子が、扁平上皮がんに高発現し、腫瘍形成、浸潤に重要な役割を果たすことも見いだすとともに、その結合タンパク質のがん進展における役割について明らかにすることができた。さらにこの結合を阻害する戦略を開発することにより、新たながん治療法へ応用することができると考えている。
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