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

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。已有研究报道人乳腺癌组织中DDR1的表达水平高于正常乳腺组织，本研究在体外检测了人T-47D乳腺癌细胞中DDR1mRNA和蛋白的表达。我们利用载体表达小发夹状RNA(ShRNA)的RNA敲除方法鉴定了DDR1在T-47D细胞中的作用，抑制了DDR1在T-47D细胞中的表达，减少了对胶原蛋白包裹的平板的黏附。在形态学上，抑制T-47D细胞中的DDR1减少了胶原涂层平板上的伪足延伸。抑制T-47D细胞中的DDR1减少了通过胶原网的迁移。在含有可溶性胶原的情况下，抑制T-47D细胞中的DDR1会降低CDC-42的活性。DDR1与细胞外基质中的胶原蛋白相互作用，导致乳腺癌细胞在间质组织微环境中迁移。

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.