The inhibition of P97 in osteosarcoma cells was found to inhibit the ERAD pathway, allowing the accumulation of unfolded proteins in cells, and subsequently activate PERK- and IRE1-related UPR pathways, namely the IRE1α-XBP1s-CHOP pathway and the PERK-eIF2α-ATF4-CHOP pathway, to promote protein degradation and apoptosis [53]. This evidence concerns the gene ERN1 and osteosarcoma.