Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation

  • Chen, Feng (State Key Laboratory of Infectious Disease Diagnosis and Treatment First Affiliated Hospital College of Medicine, Zhejiang University) ;
  • Zhu, Hai-Hong (State Key Laboratory of Infectious Disease Diagnosis and Treatment First Affiliated Hospital College of Medicine, Zhejiang University) ;
  • Zhou, Lin-Fu (Department of Cell Biology College of Medicine, Zhejiang University) ;
  • Wu, Shan-Shan (State Key Laboratory of Infectious Disease Diagnosis and Treatment First Affiliated Hospital College of Medicine, Zhejiang University) ;
  • Wang, Jing (State Key Laboratory of Infectious Disease Diagnosis and Treatment First Affiliated Hospital College of Medicine, Zhejiang University) ;
  • Chen, Zhi (State Key Laboratory of Infectious Disease Diagnosis and Treatment First Affiliated Hospital College of Medicine, Zhejiang University)
  • Accepted : 2010.04.30
  • Published : 2010.07.31
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Abstract

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58% of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells, we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.

Keywords

References

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