a College of Medical, Veterinary and Life Sciences , University of Glasgow , Glasgow , UK.
b Department of Internal Medicine , Ashtead Hospital , Ashtead , UK.
Cancer Biol Ther. 2019;20(3):349-367. doi: 10.1080/15384047.2018.1529109. Epub 2018 Nov 7.
Expression of the tumour suppressor Deleted in Colorectal Cancer (DCC) and the related protein neogenin is reduced by the mammalian serine protease chymotrypsin or the bacterial serine protease subtilisin, with increased cell migration. The present work examines whether these actions are associated with changes in the expression of cadherins, β-catenin and vimentin, established markers of the Epithelial-Mesenchymal Transition (EMT) which has been linked with cell migration and tumour metastasis. The results confirm the depletion of DCC and neogenin and show that chymotrypsin and subtilisin also reduce expression of β-catenin in acutely prepared tissue sections but not in human mammary adenocarcinoma MCF-7 or MDA-MB-231 cells cultured in normal media, or primary normal human breast cells. A loss of β-catenin was also seen in low serum media but transfecting cells with a dcc-containing plasmid induced resistance. E-cadherin was not consistently affected but vimentin was induced by low serum-containing media and was increased by serine proteases in MCF-7 and MDA-MB-231 cells in parallel with increased wound closure. Vimentin might contribute to the promotion of cell migration. The results suggest that changes in EMT proteins depend on the cells or tissues concerned and do not parallel the expression of DCC and neogenin. The increased cell migration induced by serine proteases is not consistently associated with the expression of the EMT proteins implying either that the increased migration may be independent of EMT or supporting the view that EMT is not itself consistently related to migration. (241).
肿瘤抑制因子Deleted in Colorectal Cancer（DCC）和相关蛋白neogenin 的表达可被哺乳动物丝氨酸蛋白酶糜蛋白酶或细菌丝氨酸蛋白酶枯草杆菌蛋白酶降低，同时增加细胞迁移。本研究检查这些作用是否与细胞间黏附分子（E-cadherin）、β-连环蛋白和波形蛋白表达的变化有关，这些蛋白是上皮-间质转化（EMT）的标志性蛋白，与细胞迁移和肿瘤转移有关。结果证实 DCC 和 neogenin 的耗竭，并表明糜蛋白酶和枯草杆菌蛋白酶还降低了急性组织切片中β-连环蛋白的表达，但不降低在正常培养基中培养的人乳腺腺癌 MCF-7 或 MDA-MB-231 细胞或原代正常人乳腺细胞中的表达。β-连环蛋白的缺失也见于低血清培养基中，但用含有 dcc 的质粒转染细胞可诱导其产生抗性。E-钙黏蛋白不总是受到影响，但波形蛋白在低血清培养基中被诱导，并与 MCF-7 和 MDA-MB-231 细胞中丝氨酸蛋白酶诱导的伤口闭合增加平行增加。波形蛋白可能有助于促进细胞迁移。结果表明，EMT 蛋白的变化取决于所涉及的细胞或组织，并不与 DCC 和 neogenin 的表达平行。丝氨酸蛋白酶诱导的细胞迁移增加并不总是与 EMT 蛋白的表达一致，这意味着增加的迁移可能独立于 EMT，或者支持 EMT 本身与迁移并不总是相关的观点。（241）。
