Fig. 6
From: Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
CAF-mediated therapeutic resistance in anticancer treatment. a CAFs secreted dense desmoplastic matrix, including laminin A1, type IV collagen into the TME hindering the delivery of drugs, and increasing the resistance. b CAFs released regulatory molecules such as periostin, Nodal, EGF, IGF-2, and IL-6 or exosomes, which activated pro-survival signaling pathways, including proliferation, stemness, and apoptosis of cancer cells enhancing therapeutic resistance. c CAFs fed increased pyruvate, lactate, or GSSG to tumor cells by increasing energy supply and decreasing ROS. It also activated IGF-2 to increase autophagy via downstream pathways and the changes of metabolism in CAFs and tumor cells maintain the tumor survival in treatment. d CAFs released regulatory factors, including IGF-1, HGF, CXCL12, IL-6, and TGF-β1, to mediate EMT process through downstream ANAX2 and p38 pathways, subsequently increasing metastasis and resistance. TG2 tissue transglutaminase 2, LAMA1 laminin A1, Bcl-2 B cell lymphoma 2, Bax Bcl-2-associated X protein, Sox-2 SRY (sex-determining region Y)-box 2, TCA cycle tricarboxylic acid cycle, PP2A protein phosphatase 2A, CRM1 chromosomal region maintenance 1, GSSG glutathione disulfide, GSH glutathione, ANXA2 annexin A2
