Fig. 1

Schematic diagram showing the effects of CAFs on cancer cell metastatic behavior. a) Activated fibroblasts (NAF) originate from normal fibroblasts (NF) upon exposure to inflammatory cytokines. Following contact with cancer cells, they can originate the cancer-associated fibroblasts (CAFs) with enhanced proliferative and paracrine potential. The paracrine activity of CAFs and cancer cells underlying the bidirectional crosstalk between the two cell populations with the specific involved deregulated pathways are depicted. The arrows indicate the stimulatory effect of each cytokine. The induction of EMT in cancer cells relies on the activation of transcription factors, lncRNAs and epigenetic changes. b) CAFs-mediated effect on mesenchymal-independent (cancer cells maintain an epithelial-like phenotype) invasive potential. Different strategies are adopted by CAFs to facilitate cancer cells invasion of ECM, thus favoring their metastatic potential. Among these, we find the co-migration, by which CAFs and cancer cells migrate together thanks to the expression of cell membrane junctions; the ECM digestion that consists in the production of proteases by CAFs that is accompanied by the release of chemokines acting as chemoattractants for cancer cells; the force-mediated ECM remodeling that consists in the augmented contractility of the ECM and the concomitant alignment of Fibronectin (Fn), thus offering to the cancer cells a preferential route in the invasive process