Program in Cell and Molecular Biology and the Department of Urology, University of Michigan, Ann Arbor.
Front Biosci (Landmark Ed). 2012 Jan 1;17(5):1948-64. doi: 10.2741/4031.
Epithelial (E)-cadherin is a homophilic adhesion molecule which is responsible for maintenance of baso-lateral cell adhesion and polarity. E-cadherin can be lost from the cell surface by proteolytic cleavage, resulting in the generation of an 80kDa fragment referred to a soluble E-cadherin (sE-cad). Although originally discovered in the conditioned media of breast cancer cells and later verified in the fluids of cancer patients, today sE-cad has been reported in patients with viral and bacterial infections, organ failure, and benign disease. The proteases implicated in this cleavage event include members of the disintegrin family (ADAM10 and 15), bacterial proteases (gingipains and BFT), cathepsins (B, L, S), matrix metalloproteases (MMP-2, 3, 7, 9, and 14), Kallikrein-7 (KLK7), and plasmin. Stimulus that induces sE-cad generation by ADAMs, MMPs, KLK7, and plasmin in vitro ranges from serum withdrawal to pro-inflammatory cytokines to growth factors. The cellular or physiologic consequences of sE-cad accumulation include the disruption of adherens junctions, cellular migration and invasion, induction of MMPs, as well as cell signaling, suggesting that sE-cad may contribute to disease progression.
上皮细胞（E）-钙黏蛋白是一种同型黏附分子，负责维持基底外侧细胞黏附和极性。E-钙黏蛋白可通过蛋白水解切割从细胞表面丢失，从而产生 80kDa 的片段，称为可溶性 E-钙黏蛋白（sE-cad）。尽管最初在乳腺癌细胞的条件培养基中发现，后来在癌症患者的体液中得到证实，但如今在病毒和细菌感染、器官衰竭和良性疾病患者中也已报告 sE-cad 的存在。参与这种切割事件的蛋白酶包括解整合素家族成员（ADAM10 和 15）、细菌蛋白酶（gingipains 和 BFT）、组织蛋白酶（B、L、S）、基质金属蛋白酶（MMP-2、3、7、9 和 14）、激肽释放酶-7（KLK7）和纤溶酶。体外诱导 ADAMs、MMPs、KLK7 和纤溶酶产生 sE-cad 的刺激因素范围从血清剥夺到促炎细胞因子到生长因子。sE-cad 积累的细胞或生理后果包括黏着连接的破坏、细胞迁移和侵袭、MMP 的诱导以及细胞信号转导，这表明 sE-cad 可能有助于疾病进展。
