CAFs promote tumorigenesis: a schematic illustration representing all the fronts in which CAFs boost cancer. By secreting soluble factors and lipid-based particles, transformed epithelium drives recruitment (1) and reprogramming (2) of several types of cells into CAFs, including resident fibroblasts (NAFs) that are naturally tumor-suppressive. CAFs are then activated to promote tumor initiation (3), cancer cell stemness (4), and to change tumor metabolism (5) by intensive cross talk of ligands/receptors, cell–cell contact, and remodeling the ECM (6). Concomitantly, CAFs prevent immune surveillance of tumor cells (7) while balancing inflammation and angiogenesis (8). Finally, CAFs stimulate invasion and metastasis by facilitating tumor cell dissemination, intra- and extravasation, and metastatic colonization (9).