Fig. 1
From: Intimate communications within the tumor microenvironment: stromal factors function as an orchestra
CAFs regulate tumor progression and therapeutic response. Our recent work demonstrated that CAFs promote tumor progression and therapeutic resistance through diverse mechanisms. CAFs secrete IL6 and IL8, which activate the JAK2-STAT3 pathway. JAK2-dependent phosphorylated BRD4 interacts with STAT3 to modulate chromatin remodeling (enhancer/super-enhancer reprogramming) and promote oncogene expression, leading to BETi resistance and tumor progression. IL6 also induces LRG1 expression through STAT3-dependent transactivation, which promotes EMT and metastasis. CAF-secreted TGF-β2 induced the expression of GLI2, which synergizes with hypoxia-induced HIF1α to promote CRC stemness and chemoresistance