We can hypothesize that the negative feedback exerted by LOXs is effective in normal conditions, but as dysregulation of TGF-β-signaling manifests in tumor tissue, an increase in ECM deposition and LOXs also occurs; as a consequence, the ECM stiffness also increases leading to additional release of TGF-β from the extracellular deposit and further dysregulation, thus sustaining a vicious circle. This evidence concerns the gene TGFB1 and neoplasm.