This potential redundancy is critically important, given that genetic loss of XIAP causes both very early onset inflammatory bowel disease and X-linked lymphoproliferative syndrome 2 (XLP-2) and that the overexpression of cIAP1 and cIAP2 is linked to both carcinogenesis and chemotherapeutic resistance.
Western blot analysis indicated that CPNE1 silencing downregulated the expression of many proteins associated with tumorigenesis and development, including Ras, MEK-1/2, WNT1, β-catenin, cyclin A1, IRAK2 and cIAP2.
Taken together, these results demonstrate that Pellino-1 contributes to lung oncogenesis through the overexpression of cIAP2 and promotion of cell survival and chemoresistance.
Copy number loss for and somatic mutation of BIRC2 and BIRC3 have been frequently detected in lymphoid malignancies, with such genetic alterations being thought to contribute to carcinogenesis through activation of the noncanonical NF-κB signaling pathway.
Recent studies have identified new recurrent mutations in CLL cells, including mutation of the gene encoding one of the spliceosome subunits, SF3B1, mutation or rearrangement of NOTCH1, a gene of well-known tumorigenesis association, and disruption of BIRC3, a member of the inhibitors of apoptosis (IAP) family.
Our observations strongly suggest that IAP-1 is at least partly responsible for promoting carcinogenesis and mediating resistance to cisplatin in many MPM tumors and that further study of this apoptotic pathway is warranted.