Hepatocellular carcinoma (HCC) is a devastating consequence of chronic inflammatory liver diseases. The underlying molecular mechanisms for the relationships between HCC and chronic inflammatory are needed to be completely elucidated. TLR4 exhibit different sides with regard to the roles in the regulation of carcinogenesis and tumor progression. Researchers discovered that genetic or pharmacology blocking of TLR4 increases susceptibility to DEN-induced HCC development. TLR4 mutation results in suppressed immune networks, a halt of cellular senescence induction in TLR4 mutant liver tissue, which promotes proliferation and suppresses programmed cell death. Moreover, TLR4 mutation results in a suppressed capacity of DNA repair due to a decrease in TLR4-medicated expression of DNA repair proteins Ku70/80 in liver tissue and cells. Isotopic expression of Ku70 in TLR4 mutant mouse restores senescence and interrupts the positive feedback loop of DNA damage and oxidative stress, which reverses TLR4 mutation-deteriorated HCC carcinogenesis. These results were recently published in theHepatology (2013/1/8 online).
This work was directed by Prof. Hu Zhuowei, a Principle Investigator of the State Key Laboratory of Bioactive Substance and Function of Natural Medicines in IMM (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College). His group is mainly focused on the molecular mechanism of immunity and chronic diseases, such as cancer and tissue fibrosis.
Original Article:http://onlinelibrary.wiley.com/doi/10.1002/hep.26234/abstract;jsessionid="5EC7147256D6BB9973AA24469742D0C0.d02t03
