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

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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.