CD44 and cancer: With tumors malignant progression, the genome often accumulates mutations in the TGF-β receptor system, rendering cancer cells unresponsive to TGF-β.[84] This converts TGF-β into tumor promoters, resulting in increased invasion and metastasis.[85] MMP9 is secreted to the surface of cells by binding with the surface receptor CD44, and then proteolysis activates TGF-β.[86] In addition, MMP2, MMP9, and MMP14 indirectly regulate the bioactivity of TGF-β by cutting off the potential TGF-β binding protein 1 (LTBP-1) of the ECM component, and dissolving the ECM-bound TGF-β.[87,88]