Regulation of adhesion and migration of cancer cells by tyrosine kinase signaling

在该项目中，鉴定了在癌症恶性进展期间被酪氨酸磷酸化的蛋白质的数量，并进行了功能分析。CDCP 1被鉴定为参与癌细胞的锚定非依赖性生长的分子，也调节细胞迁移和基质降解。在临床样本中，具有高水平CDCP 1表达的肺和胰腺肿瘤亚组显示出比具有低水平CDCP 1表达的亚组具有统计学上更差的预后。研究表明，ephrin-B1控制多种与转移相关的因素，如细胞-细胞相互作用和迁移，并且阻断ephrin-B1信号传导的肽在体内抑制胃癌的腹膜扩散。一种新的蛋白质Ossa被鉴定为在腹膜播散过程中酪氨酸磷酸化的分子，被证明是获得对氧化应激诱导的细胞凋亡的抵抗所必需的。

In this project, numbers of proteins which are tyrosine-phosphorylated during the malignant progression of cancers were identified and functional analysis was performed. CDCP1, which was identified as a molecule involved in anchorage independent growth of cancer cells, also regulates cell migration and matrix degradation. A subset of lung and pancreatic tumors which has high levels of CDCP1 expression showed statistically worse prognosis than that with low levels of CDCP1 expression in clinical samples. It was demonstrated that ephrin-B1 controls multiple factors associated with metastasis such as cell-cell interaction and migration, and peptides which block ephrin-B1 signaling suppressed the peritoneal dissemination of gastric cancers in vivo. A novel protein Ossa identified as a molecule tyrosine-phosphorylated during peritoneal dissemination was shown to be essential for acquireing resistance to the oxidative stress-induced apoptosis.