Analysis of the function and sigial transduction about Discoidin Domain Receptor (DDR)1 as a unique collagen receptor.

盘状蛋白结构域受体（DDR）1作为一种独特的胶原蛋白受体的功能和信号转导分析。

• 批准号: 14571147
• 负责人: ISHIKO Takatoshi
• 金额: $ 2.11万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571147/
• 关键词: DDR1; collagen; signal transduction

Discoidin Domain Receptor (DDR)1 is a receptor tyrosine kinase activated by collagen that is abundant in extracellular matrix. Previous studies reported human mammary carcinoma tumors expressed DDR1 highly in comparison with normal mammary tissues.In the present study, we detected DDR1 mRNA and protein in human T-47D mammary carcinoma cells in vitro. We used RNA knock down method by vector expressing small hairpin RNA(shRNA) to identify the role of DDR1 in T-47D cells.Suppression of DDR1 in T-47D cells decreased adherence to collagen-coated plates. Morphogically, suppression of DDR1 in T-47D cells decreased exhibition of pseudopod extension on collagen-coated plates. Suppression of DDR1 in T-47D cells decreased migration through collagen lattices. Suppression of DDR1 in T-47D cells decreased activity of cdc-42 in the presence of soluble collagen.Taken together, the interaction of DDR1 with collagen of extracellular matrix results in migration in a stromal tissue microenvironment in mammary carcinoma cells.

盘状结构域受体 (DDR)1 是一种由细胞外基质中丰富的胶原蛋白激活的受体酪氨酸激酶。既往研究报道，与正常乳腺组织相比，人乳腺癌肿瘤高表达DDR1。在本研究中，我们在体外检测了人T-47D乳腺癌细胞中DDR1 mRNA和蛋白。我们使用表达小发夹RNA（shRNA）的载体进行RNA敲低方法来鉴定DDR1在T-47D细胞中的作用。T-47D细胞中DDR1的抑制降低了对胶原包被板的粘附。从形态上看，T-47D 细胞中 DDR1 的抑制减少了胶原包被板上伪足延伸的表现。 T-47D 细胞中 DDR1 的抑制减少了通过胶原蛋白晶格的迁移。在可溶性胶原蛋白存在的情况下，T-47D 细胞中 DDR1 的抑制降低了 cdc-42 的活性。综上所述，DDR1 与细胞外基质胶原蛋白的相互作用导致乳腺癌细胞在基质组织微环境中迁移。