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取得了很大的进展，并强调了这一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，通过接头蛋白Grb2将RTK连接到CDM RAC交换因子DOCK4。在NIH3T3细胞中，DOCK4是依赖血小板衍生生长因子的细胞迁移和血小板衍生生长因子受体β(PDGFFRβ)内吞所必需的。在HCT116细胞中，DOCK4是依赖EGF的细胞迁移和EGFR内吞所必需的。此外，DOCK4的表达与肿瘤的侵袭深度和转移成正比。这些数据可能表明DOCK4是一种潜在的肿瘤进展调节因子

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