Abstract:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the members of the tumor necrosis factor (TNF) superfamily. It can activate the apoptosis signaling pathways through engagement of the specific death receptors (DR4) or (DR5) in a broad range of cancer cell lines but not in normal cells. Thus, TRAIL is a potential anti-cancer agent. However, a small number of cancer cells may escape TRAIL induced cell death, and become resistant to it. For instance, targeted deletion of bax gene in human colorectal cancer cell line HCT116 (HCT116 bax-/-) renders the cells resistant to TRIAL induced apoptosis. In this project, we used gene-targeting technology CRISPR/Cas9 system to knock out the XIAP gene in HCT116 bax-/- cells. We showed that, as predicted, the loss of XIAP led to HCT116 bax-/- cells to overcome TRAIL resistance caused by bax deletion. This finding is significant for future study of the molecular mechanism behind cancer cell resistance to TRAIL and may help future personalized anti-cancer treatment.
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