Figure 7.
SRSF1 promotes pancreatitis and KRASG12D-mediated pancreatic cancer, and its downregulation is involved in negative feedback to KRASG12D to maintain cellular homeostasis. Splicing factor SRSF1 downregulation is a negative-feedback cellular response to KRASG12D mutation, which dampens MAPK signaling activity and contributes to pancreas-cell homeostasis. Conversely, increased SRSF1 enhances MAPK signaling through alternative splicing of Il1r1 pre-mRNA, promoting pancreatitis and ADM, thus accelerating KRASG12D-mediated tumorigenesis. One mechanism of SRSF1 upregulation is transcriptional activation by MYC, which can be amplified or epigenetically activated (↑).