Fig. 1.

Conversion from normal fibroblasts (NFs) to cancer-associated fibroblasts (CAFs). a Grow factors and cytokines such as transforming growth factor-beta 1 (TGF-β1), osteopontin (OPN), and IL-1β combined with their reporters in NFs, then activated the downstream effector including miRNAs and CD44, etc. to regulate the targeted gene expression of CAFs through TGF-β/Smads and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. b Cancer-derived exosomes shuttling cargos such as miRNAs and lncRNAs transformed NFs to CAFs via the downstream signals including TGF-β/Smads, Janus kinase/signal transducers and activators of transcription (JAK/STAT), NF-κB and mitogen-activated protein kinase (MAPK) cascades. c NF-CAF conversion was driven by glucose metabolism reprogramming and hypoxia-inducible factor-1α (HIF-1α) signaling pathway was implicated in this glycolysis. d Changes in cellular homeostasis triggered the self-propelled conversion by regulating the cytoskeletal proteins activation and secreted phenotype through the JAK/STAT and p53 signaling pathways. Fli-1 leukemia integration 1, TCF12 transcription factor 12, SOCS1 suppressor of cytokine signaling 1, B4GALT3 β-1,4-galactosyltransferases III, IGF2R insulin-like growth factor 2 receptor, LPA lysophosphatidic acid, VDAC voltage-dependent anion channel, YAP1 Yes-associated protein 1, TEAD1 TEA domain transcription factor-1, SDF-1 stromal cell-derived factor-1, also known as CXCL12, EREG epiregulin, ROS reactive oxygen species