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首页> 外文期刊>Oncogene >The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1
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The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1

机译：CEACAM1介导的凋亡途径被CEA激活并触发CEACAM1的双重切割

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Marked reduction in apoptosis is a hallmark of early colon tumour growth and the vast majority of these tumours exhibit a loss of expression of the glycoprotein carcinoembryonic-antigen-related cell adhesion molecule 1 (CEACAM1). We recently reported that the CEACAM1 functions as a mediator of apoptosis implicating this cell surface protein in early tumour development. However, the mechanistic involvement of CEACAM1 in cell death pathways is unclear. Here, we show that apoptosis triggers cleavage of the long form of CEACAM1 (CEACAM1-4L) at intracellular and extracellular sites in Jurkat cells and HEK293 cells. Signalling through CEACAM1 leads to caspase activation including caspase-1 and -3 and also involves non-caspase proteases. Moreover, we provide evidence that the naturally occurring CEACAM family member CEA is an inducer of CEACAM1-mediated apoptosis in HT29 colon cancer cells, an effect that depends on the abundance of CEACAM1 on the cell surface. Together, our results demonstrate that the CEACAM1-dependent cell death pathway involves dual cleavage of CEACAM1 and caspase activation and can be activated by CEA.
机译：凋亡的明显减少是早期结肠肿瘤生长的标志，这些肿瘤中的绝大多数表现出糖蛋白癌胚抗原相关细胞粘附分子1（CEACAM1）的表达缺失。我们最近报道，CEACAM1作为凋亡的介质，在早期肿瘤发展中牵涉该细胞表面蛋白。但是，尚不清楚CEACAM1是否参与细胞死亡途径。在这里，我们显示凋亡在Jurkat细胞和HEK293细胞的细胞内和细胞外部位触发长形式CEACAM1（CEACAM1-4L）的切割。通过CEACAM1发出的信号导致caspase激活，包括caspase-1和-3，还涉及非caspase蛋白酶。此外，我们提供的证据表明，天然存在的CEACAM家族成员CEA是HT29结肠癌细胞中CEACAM1介导的细胞凋亡的诱导剂，这种作用取决于细胞表面上CEACAM1的丰度。在一起，我们的结果表明，依赖CEACAM1的细胞死亡途径涉及CEACAM1和caspase激活的双重裂解，并可以被CEA激活。

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