Fig. 8: Schematic representation of the tumour suppressive role of iASPP in PC.
From: p53 inhibitor iASPP is an unexpected suppressor of KRAS and inflammation-driven pancreatic cancer
iASPP is a paradoxical suppressor of tumour initiation in PDAC: although iASPP binds to and inhibits previously-identified tumour suppressive p53 and NF-κB/p65 pathways, iASPP additionally binds to JunD/AP1 and inhibits this inflammatory, oncogenic axis. Whilst the NF-κB/p65 pathway has been shown to be tumour suppressive, it is possible that its upregulation of the inflammatory response confers a dual and conflicting role in contributing to tumour initiation. Mutation of p53 (p53R172H) or deletion of iASPP (iASPPΔ8/Δ8) on a KRASG12D background leads to cancer initiation and likely does so through a similar pathway, as evidenced by the altered expression of an extensively overlapping gene set, comprised primarily of NF-κB and AP1-regulated inflammatory genes. The absence of iASPP in addition to p53 mutation leads to an acceleration of KRASG12D-driven PDAC onset.
