FIGURE 5.

Summarizing cartoon of our findings combined with data published by other groups before. CD44 is cleaved by ADAM10 to generate a CD44 C-terminal fragment (CD44 CTF). This CTF is then prone to y-secretase (y-sec) cleavage within the membrane, which generates a CD44 intracellular domain (CD44 ICD). This ICD translocates to the nucleus and induces the expression of e.g. MMP14, MMP2 and MMP9. At the cell surface CD44, MMP14, MMP2, MMP9 and the tissue inhibitor of metalloproteinases 2 (TIMP2) form a multi-protein complex and attach to intracellular F-actin. This complex influences cell-cell and cell-matrix contacts and thereby changes cell migration, spheroid formation and attachment to hyaluronan.