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The mechanisms of hepatocarcinogenesis by loss of LKB1

Research Project

Project/Area Number 20790304
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionKyoto University

Principal Investigator

DEGUCHI Atsuko  Kyoto University, 医学研究科, 研究員 (10422932)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords腫瘍 / 肝細胞癌 / シグナル伝達 / LKB1 / キナーゼ / 癌
Research Abstract

The serine/threonine protein kinase LKB1 is a tumor suppressor gene mutated in the Peutz-Jeghers syndrome patients. The mutations are found also in several types of spDradic cancer. We have previously shown that the heterozygous Lkbl mutations in mice cause gastrointestinal hamartomas after 20 weeks of age, and hepatocellular carcinomas (HCC) after 50 weeks. However, the mechanisms of hepatocaricinogenesis by LKB1 loss have not been elucidated. In this study, we found that expression of c-Jun was increased by LKB1 loss. In addition, we investigated the effect of LKB1 on cell motility whose acquisition occurs in early metastasis. We found that knockdown of LKB1 enhanced cell migration and PAK1 activity in human colon cancer HCT116 cells. Furthermore, we found that PAK1 was activated in the hepatocellular carcinomas and the precancerous liver lesions of Lkbl (+/-) mice. Taken together, these results suggest that PAK1 is a direct downstream target of LKB1 and plays an essential role in LKB1-induced suppression of cell migration.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (7 results)

All 2009 2008 2007 2006 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (2 results)

  • [Journal Article] Hepatocellular carcinoma development by conditional b-catenin activation in Lkb1 (+/-) mice.2009

    • Author(s)
      Hiroyuki Miyoshi, Atsuko Deguchi, Yasushi Kojima, Masayuki Nakau, Masahiro Aoki, Makoto M. Taketo.
    • Journal Title

      Cancer Sci. 100

      Pages: 2046-2053

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocellular carcinoma development by conditional β-catenin activation in Lkb1 (+/-) mice2009

    • Author(s)
      Miyoshi H., et al.
    • Journal Title

      Cancer Science 100

      Pages: 2046-2053

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of protein kinase G increases the expression of p21 CIP1, p27KIP1 and histidine triad protein through Sp1.2008

    • Author(s)
      Cen B, Deguchi A, Weinstein IB.
    • Journal Title

      Cancer Res 68

      Pages: 5355-5362

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of protein kinase G Increases the expression of p21CIP1, p27KIP1, and histidine triad protein 1 through Sp12008

    • Author(s)
      Cen B, et.al.
    • Journal Title

      Cancer Research 68

      Pages: 5355-5562

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LKB1 suppresses p21-activated kinase-1 (PAK1) by phosphorylating at Tht109 in the p21-binding domain.

    • Author(s)
      Atsuko Deguchi, Hiroyuki Miyoshi, Yasushi Kojima, Katsuya Okawa, Masahiro Aoki, Makoto M. Taketo.
    • Journal Title

      J. Biol. Chem. (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Presentation] Gene expression profiles of hepatocellular carcinoma in Lkb1 (+/-) mice.2007

    • Author(s)
      Deguchi A, Miyoshi H, Kojima Y, Taketo MM.
    • Organizer
      International Symposium 2007
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2009 Final Research Report
  • [Presentation] Gene expression profile s of hepatocellular carcinoma in Lkb1 (+/-) mice.2006

    • Author(s)
      Deguchi A, Miyoshi H, Kojima Y, Taketo MM
    • Organizer
      21st Century COE Colloquium Animal models for Cancer Research
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2009 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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