Involvement of DNA Damage Response Pathways in Hepatocellular Carcinoma
Table 2
Roles of DNA DSB repair proteins in HCC.
DSB repair related proteins
Functions
Reference
p53 binding protein 1 (53BP1)
53BP1 enhances TP53-mediated transcriptional activation via binding on DBD of TP53. 53BP1 is also used as an indicator of DNA damage and has been shown to rapidly localize to regions of DNA double-strand breaks. 53BP1 has a binding site for phosphorylated H2AX and colocalizes with phosphorylated H2AX at sites of damage.
H2AX is a potential regulator of DNA repair and is a useful tool for detecting DNA damage, which also frequently occurs in preneoplastic lesions of HCC.
Toll-like receptor 4 (TLR4) protects against HCC carcinogenesis by enhancing the expression and function of DNA repair protein Ku70. Ectopic expression of Ku70 protects against HCC initiation and progression by restoring the cellular senescent response, decreases DNA damage, and promotes programmed cell death in TLR4-deficient livers.
Overexpression of Ku80 obviously inhibits cell proliferation ability of HCC cells, SMMC7721, in vitro and in vivo, through functions as a tumor suppressor by inducing S-phase arrest in a TP53-dependent pathway.
Tissue staining results showed that the highest ratio of DNA-PKcs positive expressing cells was detected in HCC than in cholangioadeno carcinomas biliary cystadenocarcinomas.
Autophosphorylation of ATM at S1981 extends activations of DNA damage signaling pathways to reach S phase arrest in HepG2 cells. Inhibited activity of ATM improves the cytotoxicity of taxol and serafenib in HepG2 cells.
