RegulationB of colon cancer progression by CDM protein DOCK4

生长因子受体酪氨酸激酶（RTKs）抑制剂在癌症中的临床研究已经获得了很多希望，并强调了该途径在肿瘤生物学中的重要性。我们提出了一种新的细胞内信号通路，通过适配器蛋白Grb2将RTK与CDM Rac交换因子DOCK4连接起来。在NIH3T3细胞中，DOCK4是PDGF依赖性细胞迁移和PDGF受体β(PDGFRβ)内吞所必需的。在hct116细胞中，DOCK4是egf依赖性细胞迁移和EGFR内吞作用所必需的。此外，DOCK4的表达与侵袭深度和转移成正比。这些数据可能表明DOCK4是肿瘤进展的潜在调节因子

Clinical studies with growth factor receptor tyrosine kinases (RTKs) inhibitors in cancer have met with a lot of promise and underscore the importance of this pathway in tumor biology. We present evidence for a novel intracellular signaling pathway linking RTK to the CDM Rac exchange factor DOCK4 via adaptor protein Grb2. In NIH3T3 cells, DOCK4 is required for PDGF dependent cell migration and PDGF receptorβ(PDGFRβ) endocytosis. In HCT116cells, DOCK4 is required for EGF-dependent cell migration and EGFR endocytosis. In addition, DOCK4 expression is increased in proportion to invasion depth and metastasis. These data may indicate that DOCK4 is a potential regulator of tumor progressio