Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

Figure 1 The cellular origins of cancer-associated fibroblasts in solid tumors and colorectal cancer. (1) Colon resident fibroblasts, intestinal mesenchymal cells and mesenchymal stem cells are converted to cancer-associated fibroblasts (CAFs) by stimulation of different activators including stroma-derived factor 1, transforming growth factor beta (TGF-β), TGF-β1, C-X-C chemokine ligand 12, reactive oxygen species, and the Notch and Akt signaling pathways; (2) Monocytes are transformed to CAF through monocyte-myofibroblast transdifferentiation; (3) Pericytes, adipocytes and smooth muscle cells are transformed to CAF by stimulation of the activators TGF-β1 and Wnt-3a; and (4) Epithelial cells, mesothelial cells, tumor cells are transformed into CAF through the process of epithelial mesenchymal transition by stimulation of the activator TGF-β1, endothelial cells are transformed into CAF by the process of endothelial-mesenchymal transition by stimulation of the TGF-β activator. In addition to all these factors involved in myofibroblast activation, interleukin 1 β (IL-1β), IL-6 through nuclear factor kappa B, and Janus kinase have been reported to function as transducers and activators of the signal transducer and activator of transcription 3 to promote CAF activation. Created with BioRender.com. TGF-β: Transforming growth factor beta; IMC: Intestinal mesenchymal cells; MSCs: Mesenchymal stem cells; CAFs: Cancer-associated fibroblasts; CXCL12: C-X-C chemokine ligand 12; IL: Interleukin; NF-κB: Nuclear factor kappa B; SDF-1: Stroma-derived factor 1; ROS: Reactive oxygen species.