Opposite roles of furin and PC5A in N-cadherin processing.

摘要: We recently demonstrated that lack of Furin-processing the N-cadherin precursor (proNCAD) in highly invasive melanoma and brain tumor cells results cell-surface expression a nonadhesive protein favoring cell migration invasion vitro. Quantitative polymerase chain reaction analysis malignant human revealed all proprotein convertases (PCs) only levels Furin PC5A are modulated, being inversely (Furin) or directly (PC5A) correlated with capacity. Intriguingly, N-terminal sequence following Furin-activated NCAD site (RQKR↓DW(161), mouse nomenclature) reveals second putative PC-processing (RIRSDR↓DK(189)) located first extracellular domain. Cleavage at this would abolish adhesive functions because loss critical Trp(161). This was confirmed upon fate endogenous prosegment proNCAD glioma expressing high low (U343) negligible (U251). Cellular analyses is best activating convertase releasing an ~17-kDa prosegment, whereas major inactivating enzyme resulting secretion ~20-kDa product. Like surface, cleavage molecule RIRSDR↓DK(189) renders U251 cancer less to one another more migratory. Our work modifies present view on posttranslational processing surface classic cadherins clarifies how possesses range potentials plays role progression.