1. Kor /
  2. Eng

  1. Kor /
  2. Eng

Major AchievementsFollowings are the major outstanding achievements of the SAIHST faculties

[김성주 교수/우수논문] J Hepatol. 2015 Jan;62(1):121-30. doi: 10.1016/j.jhep.2014.08.007. Epub 2014 Aug 15.
No 16
Date 2016/04/19





김성주 교수

(의과대학 외과학, SAIHST 겸직)


Impact Factor ('13) = 10.401



J Hepatol. 2015 Jan;62(1):121-30. doi: 10.1016/j.jhep.2014.08.007. Epub 2014 Aug 15.


SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma.


Zhang ZY, Hong D, Nam SH, Kim JM, Paik YH, Joh JW, Kwon CH, Park JB, Choi GS, Jang KY, Park CK, Kim SJ.





SIRT1 is a class III histone deacetylase that plays diverse roles in various cancers. However, the clinical significance of SIRT1 in hepatocellular carcinoma (HCC) remains unknown. 



We analysed p53 mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC cases. None of the patients had been subjected to pre-operative treatment.




We examined 57 p53 mutations from 248 HCC tissues. Activated SIRT1 (phosphorylated form of Ser47), in the context of mutant p53, predicted a longer relapse-free survival (RFS) but not a longer overall survival (OS) (RFS: p = 0.007, OS: p = 0.280) in HCC tissues harbouring mutant p53. In multivariate analysis, activated SIRT1 remained a significant predictor of longer RFS (OR = 0.307, CI: 0.143-0.660, p=0.002). Analysis of 248 paired specimens revealed a significant correlation between activated SIRT1 (Ser47) and activated AMPK (Thr172) in HCC tissues harbouring mutant p53 (p = 0.003, n = 57). The combination of these 2 parameters was a powerful predictor for a good prognosis in these patients. In vitro, SIRT1 inactivation stimulated the growth of HCC cells, bearing mutated p53, by suppressing AMPK activity and subsequently enhancing mammalian target of rapamycin (mTOR) activity, resulting in induction of p70S6K1 activation in HCC cells. Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1.




SIRT1 exerted anti-carcinogenic effects via the AMPK-mTOR pathway in HCC in the context of mutant p53. Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression.



  김성주 교수 연구 소개  [프로필보기]  

현재 김성주 교수 연구 팀에서 수행하고 있는 실험 내용 및 방향은 다음과 같습니다.  
1. human CD34+ cell의 ex vivo와 in vivo 에서의 stemness 에 관한 연구 
2. Chapter 1의 stemness 와 관련되는 signal transduction 에 관한 연구 
3. Humanized mice의 제작 및 human T cell의 분화 
4 Humanized mice에서의 human B cell 분화 및 기능에 관한 연구 
5. Humanized mice에서의 human T cell의 tolerance 에 관한 연구 
6. Cancer cell line의 배양기술 확립 및 동물 모델 수립 
7. Primary cancer cell의 배양기술 확립 및 동물 모델 수립 
8. Humanized mice를 이용한 patient-specific therapy로의 응용 (본 연구팀의 최종 연구 목표)  


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