PI3K and MAPK Signaling Nodes Serve as Divergent Drivers of Phenotypic Plasticity in Cancer-Associated Fibroblasts in Colorectal Cancer - PubMed
12 hours ago
- #Cancer-Associated Fibroblasts
- #Signaling Pathways
- #Colorectal Cancer
- PI3K and MAPK signaling pathways drive phenotypic plasticity in colorectal cancer-associated fibroblasts (CAFs).
- Inflammatory CAFs (iCAFs) and myofibroblast-like CAFs (myCAFs) exhibit distinct functional states influenced by tumor microenvironment cues.
- PI3K/mTOR inhibition promotes iCAF formation via FGF-2 release and FGFR1-JAK2-STAT3 activation, enhancing chemokine secretion and tumor growth.
- MEK inhibition induces myCAF phenotype through interferon-dependent ROCK and JAK1 signaling, increasing ECM production and tumor colony formation.
- These findings highlight how targeted therapies can directly alter CAF phenotypes in colorectal cancer.