fig1

Figure 1. CSCs promote the activation of CAFs. Elevated ASCL2 in CSCs promotes the transcription and secretion of TGF-β, inducing the transcription of IL-6, CXCL12, and HGF, as well as the transformation of CAFs from normal fibroblasts. CSCs-derived SHH binds to PATCH1 on the CAFs and subsequently activates glutaminase (GLI) complex-mediated transcription of ACTIVIN A, LIF, and IGF1, which reciprocally maintain the stemness of CSCs. CSCs: Cancer stem cells; CAFs: cancer-associated fibroblasts; ASCL2: achaete-scute family BHLH transcription factor 2; TGF-β: transforming growth factor-β; IL-6: interleukin-6; CXCL12: chemokine (C-X-C motif) ligand 12; HGF: hepatocyte growth factor; SHH: Sonic Hedgehog; PATCH1: patched homolog 1; GLI: GLI family zinc finger; LIF: leukemia inhibitory factor; IGF1: insulin-like growth factor 1; SMO: smoothened; SMAD: mothers against decapentaplegic Homolog.