This study demonstrated that pro-survival effects by NF-κB, Akt and ERK(1/2) and anti-apoptosis actions by Six1 disrupt apoptotic functions of TRAIL-Dr4/5 pathway in ovarian cancer, which may explain why up-regulated DR4 and DR5 in ovarian cancer are associated with poor prognosis and low survival ratio of the patients.
Considering a multiple-testing-corrected significance threshold of P < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002).
GT-oligo was found to induce transcript expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR-4 and DR-5, which are generally silenced in ovarian cancer cells, rendering them insensitive to TRAIL.
Our findings indicate that c-FLIP(L) regulates sensitivity of OC to TRAIL-mediated apoptosis and offers possible therapeutical implications for OC in the future.