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Fig. 5 | BMC Cancer

Fig. 5

From: Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells

Fig. 5

Graphical representation of the potential apoptotic pathway induced by the Human-RPSA siRNA in late (DLD-1) stage colorectal cancer cell. Under normal conditions, TRF-1 and TRF-2 binds to telomeres and negatively regulates telomere length by forming the t-loop structure at the ends of chromosomes to mask the G-rich overhang. Upon siRNA-mediated knock-down of LRP/LR, TRF-2 protein expression levels are decreased, leaving the ends of chromosomes exposed and free to fuse with each other, which can lead to genetic instability. The knock-down of LRP/LR was also found to decrease telomerase activity and hTERT expression levels, causing progressive telomere shortening and the inactivation of the telomere capping function, further contributing to chromosomal end fusion and genetic instability. This leads to the G-rich overhang being exposed and recognised as a double stranded break by γH2AX. This results in the activation of the DNA damage response pathway whereby ATM kinase activated p53. This leads to the activation of several other pro-apoptotic proteins as well as the inactivation of anti-apoptotic proteins, ultimately leading to apoptotic induction

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