2012 Fiscal Year Final Research Report
Roles of small GTPase Ral in tumorigenesis
| Project/Area Number |
22501009
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Keywords | (1)低分子量GTP結合蛋白質 / (2)Ral / (3)癌 / (4)膀胱癌 |
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| Research Abstract |
Small GTPases are signaling switches acting downstream of many growth factor receptors. Their activity is regulated by the balance between positive and negative regulators, guanine nucleotide factors (GEFs) and GTPase activating proteins, respectively. Ras, an oncogene whose mutations are frequently detected in various human cancers, takes Raf, PI3 kinase, and RalGEF as direct effectors. Many reports have indicated that the signaling pathway mediated by the RalGEF-Ral pathway is important in human tumorigenesis. We have very recently identified RalGAPs for the first time (JBC, 2009). Then, we analyzed the role of RalGAP in bladder cancer progression. We reported in a paper in Oncogene, 2013 that 1) the dominant catalytic subunit of RalGAP in bladder is alpha-2 and it is strongly downregulated in invasive bladder cancer cell line compared with non-invasive cells, resulted in elevated activation of Ral in invasive cells, 2) exogenous expression of RalGAPalpha2 in invasive bladder cancer cells inhibited lung metastasis when injected to nude mice, 3) in a chemichally-induced bladder cancer model, invasive bladder cancers were detected in 42% of RalGAPalpha2-KO mice whereas none in control mice, 4) low expression of RalGAPalpha2 was correlated with poor prognosis of bladder cancer patients. Thus, reduced expression of RalGAPalpha2 is deeply associated with bladder cancer progression.
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[Journal Article] Downregulation of Ral GTPase-activating-protein causes tumor invasion and metastasis of bladder cancer2013
Author(s)
R Saito, R Shirakawa, H Nishiyama, T Kobayashi, M Kawato, T Kanno, K Nishizawa, Y Matsui, T Ohbayashi, M Horiguchi, T Nakamura, T Ikeda, K Yamane, E Nakayama, E Nakamura, Y Toda, T Kimura, T Kita, O Ogawa, H Horiuchi
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Journal Title
Oncogene 32
Pages: 894-902
Peer Reviewed
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[Journal Article] Rapid diagnosis of familial hemophagocytic lymphohistiocytosis type 3 (FHL3) by flow cytometric detection of intraplatelet Munc13-4 protein2011
Author(s)
Y. Murata, T. Yasumi, R. Shirakawa, K. Izawa, H. Sakai, J. Abe, N. Tanaka, T. Kawai, K. Oshima, M. Saito, R. Nishikomori, O. Ohara, E. Ishii, T. Nakahata, H. Horiuchi*, T. Heike
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Journal Title
Blood 118
Pages: 1225-1230
DOI
Peer Reviewed
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[Journal Article] Direct binding of RalA to PKCη and its crucial role in morphological change during keratinocytes differentiation2011
Author(s)
Y. Shirai, S. Morioka1, M. Sakuma, K.Yoshino1, C. Otsuji, N. Sakai, K. Kashiwagi, K. Chida, R. Shirakawa, H. Horiuchi, C. Nishigori, T. Ueyama, N.Saito
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Journal Title
Mol. Biol. Cell
Volume: 22
Pages: 1340-1352
DOI
Peer Reviewed
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[Journal Article] Flightless-I (Fli-I) regulates the actin assembly activity of Diaphanous-related formins (DRFs), Daam1 and mDia1, in cooperation withactive Rho GTPase2010
Author(s)
T. Higashi, T. Ikeda, T. Murakami, R.Shirakawa, M. Kawato, K. Okawa, M. Furuse, T. Kimura, T. Kita, H. Horiuchi
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Journal Title
J Biol Chem
Volume: 285
Pages: 16231-16238
DOI
Peer Reviewed
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