New Study Found Targets for Preventive Therapies in Liver Cancers
Source:
Time: 2012-10-15
Hepatocellular carcinoma (HCC) causes more than 500,000 deaths per year worldwide. Understanding early stage-specific oncogenic mechanisms is critical to develop not only diagnostic markers but also preventive strategies for HCC therapy. Now researchers from Chinese Academy of Sciences discovered a novel AP-1 dependent regulatory network specifically involved in liver cancer initiation, which provides novel strategies to develop preventive therapies for cirrhotic or post-resection patients.
Using genetic mouse models specific for liver cancer initiation, researchers led by Dr. HUI Lijian from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in collaboration with scientists from Spanish National Cancer Research Centre and Zhongshan Hospital, Fudan University found that survival of initiated cancer cells is controlled by c-Jun, through suppressing c-Fos-mediated apoptosis. Mechanistically, c-Fos induces SIRT6 transcription, which represses Survivin by reducing histone H3K9 acetylation and NF-κB activation. Importantly, using Adenovirus system, they proved that increasing SIRT6 or targeting Survivin’s anti-apoptotic activity at the initiation stage markedly impairs cancer development. Moreover, in human dysplastic liver nodules, but not in malignant tumors, a specific expression pattern with increased c-Jun-Survivin and attenuated c-Fos-SIRT6 was identified. These results reveal a regulatory network connecting stress response and histone modification in liver tumor initiation.
The study was funded by the National Science Foundation of China, Ministry of Science and Technology and Chinese Academy of Sciences. It has been published online in Nature Cell Biology on October 7th, 2012.
CONTACT:
Dr. HUI Lijian
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Email: huilab@sibcb.ac.cn
Tel: +86-21-54921329
Adenoviruses carrying SIRT6/SurT34A were injected to wild-type (WT) mice 3 days before DEN-initiation. a, TUNEL assay showed that SIRT6/SurT34A expression caused a significant increase in apoptosis 48h after DEN treatment. b, Liver tumorigenesis was quantified 12 months after DEN treatment. Each dot represents tumor quantification of an individual mouse. SIRT6 or SurT34A expression led to a significant decrease of liver cancer formation in wild-type mice (Image from Hui Lijian’s Lab).
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