RGD 基序参与 CD97/ADGRE5 促进的 HT1080 细胞黏附和活力。

The RGD motif is involved in CD97/ADGRE5-promoted cell adhesion and viability of HT1080 cells.

机构信息

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

出版信息

Sci Rep. 2019 Feb 6;9(1):1517. doi: 10.1038/s41598-018-38045-w.

CD97/ADGRE5 is an adhesion G protein-coupled receptor (aGPCR) involved in tumor cell adhesion, migration, angiogenesis, and apoptosis. CD97 has been shown previously to stimulate angiogenesis by interacting with integrins on endothelial cells via an Arginine-Glycine-Aspartic acid (RGD) motif. In this report, the role of the RGD motif in tumor cell adhesion and apoptosis was investigated using a previously-established HT1080 cell-based system. We found that the RGD motif is critical in CD97-promoted cell adhesion, in part due to the up-regulation of αvβ5 and α2β1 integrins, and that CD97 mediates its anti-apoptotic effect in extrinsic apoptosis via RGD-dependent cell adhesion. In contrast, CD97-modulated anti-apoptotic effect in intrinsic apoptosis is mediated by RGD-independent, N-cadherin-induced homotypic cell aggregation. Hence, CD97 promotes tumorigenesis via RGD-dependent and -independent mechanisms.

CD97/ADGRE5 是一种黏附 G 蛋白偶联受体（aGPCR），参与肿瘤细胞黏附、迁移、血管生成和凋亡。先前的研究表明，CD97 通过与内皮细胞上的整合素相互作用，通过精氨酸-甘氨酸-天冬氨酸（RGD）基序刺激血管生成。在本报告中，使用先前建立的 HT1080 细胞为基础的系统，研究了 RGD 基序在肿瘤细胞黏附和凋亡中的作用。我们发现，RGD 基序在 CD97 促进的细胞黏附中至关重要，部分原因是 αvβ5 和 α2β1 整合素的上调，并且 CD97 通过 RGD 依赖性细胞黏附在细胞外凋亡中发挥其抗凋亡作用。相比之下，CD97 调节的内在凋亡中的抗凋亡作用是由 RGD 非依赖性、N-钙黏蛋白诱导的同质细胞聚集介导的。因此，CD97 通过 RGD 依赖性和非依赖性机制促进肿瘤发生。