Noë V, Willems J, Vandekerckhove J, Roy F V, Bruyneel E, Mareel M
Laboratory of Experimental Cancerology, UZG, B-9000 Ghent, Belgium.
J Cell Sci. 1999 Jan;112 ( Pt 1):127-35. doi: 10.1242/jcs.112.1.127.
The E-cadherin/catenin complex, an organizer of epithelial structure and function, is disturbed in invasive cancer. The HAV (histidine alanine valine) sequence in the first extracellular domain of E-cadherin is crucial for homophilic interactions between cadherins. We report that specific peptides containing an HAV sequence interfere with the functions of the E-cadherin/catenin complex. Cells either expressing specific cadherins or not were challenged with both cadherin and noncadherin peptides comprising a central HAV sequence. Specific E-cadherin peptides inhibited cell aggregation, disturbed the epithelial morphotype and were able to stimulate invasion of cells expressing E-cadherins. Conditioned medium, containing E-cadherin fragments, also stimulated invasion in contrast to conditioned medium from which the E-cadherin fragments were removed. Our studies show that E-cadherin functions are inhibited by homologous proteolytic HAV-containing fragments that are released in an autocrine manner and subsequently inhibit the E-cadherin/catenin complex. In this way such cadherin fragments may induce and support cancer invasion.
E-钙黏蛋白/连环蛋白复合体作为上皮结构和功能的组织者，在浸润性癌中受到干扰。E-钙黏蛋白第一个细胞外结构域中的HAV（组氨酸-丙氨酸-缬氨酸）序列对于钙黏蛋白之间的嗜同性相互作用至关重要。我们报告称，含有HAV序列的特定肽会干扰E-钙黏蛋白/连环蛋白复合体的功能。用包含中央HAV序列的钙黏蛋白肽和非钙黏蛋白肽对表达特定钙黏蛋白或不表达特定钙黏蛋白的细胞进行刺激。特定的E-钙黏蛋白肽抑制细胞聚集，扰乱上皮形态型，并能够刺激表达E-钙黏蛋白的细胞侵袭。与去除了E-钙黏蛋白片段的条件培养基相比，含有E-钙黏蛋白片段的条件培养基也能刺激侵袭。我们的研究表明，E-钙黏蛋白的功能受到以自分泌方式释放的同源含HAV蛋白水解片段的抑制，这些片段随后会抑制E-钙黏蛋白/连环蛋白复合体。通过这种方式，此类钙黏蛋白片段可能诱导并支持癌症侵袭。
