The study presented here identifies at least three novel findings: (i) lactate, massively secreted by CAFs, is a trigger for the tumor-derived matrisome remodeling through the activation of the collagen prolyl-hydroxylase P4HA1 and de novo collagen I synthesis; (ii) the autocrine secretion of collagen by cancer cells is a key determinant of their invasive phenotype; (iii) the P4HA1-DDR1-STAT3 axis is the molecular pathway driving such pro-metastatic cues. Here, P4HA1 is linked to neoplasm.