Shedding light on proteolytic cleavage of CD44: the responsible sheddase and functional significance of shedding.
CD44 is the major cell-surface receptor for hyaluronan, which is implicated in cell-cell and cell-matrix adhesion, cell migration, and signaling. Studies have shown that CD44-dependent migration requires CD44 to be shed from the cell surface and that matrix metalloproteinase-mediated cleavage may provide an underlying mechanism. However, the full spectrum of proteases that may participate in CD44 shedding has yet to be defined. In this issue, Anderegg et al. demonstrate that ADAM10, but not ADAM17 or MMP14, mediates constitutive shedding of CD44 in human melanoma cells and that knockdown of ADAM10 blocks the antiproliferative activity of the soluble proteolytic cleavage product of CD44.
Experimental Pathology Division, Institut Universitaire de Pathologie CHUV, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Ivan
I
Stamenkovic
Qin
Q
Yu
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000502:physiology; D006820:Hyaluronic Acid / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism
D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D006820:Hyaluronic Acid; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D053511:Matrix Metalloproteinase 14; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human