2011 Fiscal Year Final Research Report
Functional analysis of Gli1 molecule for developing a new inclusive therapy against many tumor species
| Project/Area Number |
21390363
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
KATANO Mitsuo 九州大学, 大学院・医学研究院, 教授 (10145203)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Masafumi 川崎医科大学, 医学部, 教授 (30372741)
KUBO Makoto 九州大学, 大学病院, 助教 (60403961)
NOMURA I Masatosh 九州大学大, 学病院, 講師 (30315080)
ONISHI Hideya 九州大学, 大学院・医学研究院, 准教授 (30553276)
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| Project Period (FY) |
2009 – 2011
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| Keywords | Gli1 / Hedgehogシグナル / 膵癌 / 胃癌 / 乳癌 / 腫瘍幹細胞 / 浸潤 / 治療標的分子 |
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| Research Abstract |
Gli1 is one of target genes in the hedgehog(Hh) pathway, and Gli1 also functions as a transcriptional factor. Importantly, Gli1 is reactivated in various types of malignancies. One of reasons of overexpression of Gli1 in many cancer species may be due to crosstalk between Hh pathway and several signaling pathways such as inflammation and endocrine pathways. During this research periods, we acquired following new findings on Gli1.(1) Ligand-dependent Gli1 induction through Shh overexpression via activation of nuclear factor-kappa B pathway.(2) Suppression of Wnt pathway by Gli1 overexpression in the colon and gastric cancers.(3) Estrogen receptor pathway-dependent Gli1 induction in the breast and gastric cancers.(4) Ligand-independent but Smo-dependent Gli1 induction under hypoxic conditions.(5) Paracrine Gli1 induction through Shh produced by cancer tissue-infiltrating monocytes in the gastric cancer. We also clarified the following new biological functions of Gli1.(1) Increase of proliferation and invasion abilities in the pancreatic, breast, and gastric cancer cells.(2) Possible contribution of Gli1 to tumor initiation and/or progression in the pancreatic and breast cancers.(3) Contributions of Gli1 to drug resistance and tumorigenicity in the breast cancer stem cells. These findings indicate that Gli1 is a useful therapeutic target against not only many cancer species but also cancer stem cells.
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Research Products
(45 results)
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[Journal Article] Nuclear factor kappaB-activated monocytes contribute to pancreatic cancer progression through the production of Shh2010
Author(s)
Yamasaki A, Kameda C, Xu R, TanakaH, Tasaka T, Chikazawa N, Suzuki H, Morisaki T, Kubo M, Onishi H, Tanaka M, Katano M
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Journal Title
Cancer Immunology Immunotherapy
Volume: 59
Pages: 675-686
Peer Reviewed
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