Signal cross talks for sustained MAPK activation and cell migration: the potential role of reactive oxygen species

• Published in: Cancer and metastasis reviews Vol. 27; no. 2; pp. 303 - 314
• Main Authors: Wu, Wen-Sheng, Wu, Jia-Ru, Hu, Chi-Tan
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2008; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Movement - physiology; Enzyme Activation - physiology; Humans; Integrins - metabolism; Medical sciences; Mitogen-Activated Protein Kinases; Neoplasm Invasiveness; Non-Thematic Review; Oncology; Protein Kinase C - metabolism; Reactive Oxygen Species - metabolism; Receptor Cross-Talk - physiology; Receptor Protein-Tyrosine Kinases - metabolism; Signal Transduction - physiology; Tumors; Receptor tyrosine kinase; Reactive oxygen species; Protein kinase C; MAPK activation; Integrin; Cell migration; Oxidative stress; Enzyme; Transferases; Cell adhesion molecule; Mitogen-activated protein kinase; Cell motility; Signal transduction; Cancerology
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-008-9112-4

Signal transduction exerted by the microenvironment around the primary tumor locus may trigger tumor metastasis especially at the migration stage. Sustained mitogen activated protein kinase (MAPK) signaling involved in uncontrolled tumor cell migration rely on the cross talks between integrin, receptor tyrosine kinase (RTK) and protein kinase C (PKC). The molecular mechanisms for cross talking between these migration-related signal cascades leading to sustained cell migration are reviewed, focusing on the focal adhesion scaffold protein paxillin as the platform for signal integration. We proposed reactive oxygen species (ROS) as the critical signal messenger sustaining these signal cascades. For the cross talk of integrin with RTK, ROS may suppress paxillin-associated protein tyrosine phosphatase (PTP–PEST) relieving its negative regulatory effects. For the cross talk of integrin with PKC, PKC itself may phosphorylate integrin or paxillin-associated focal adhesion proteins to induce generation of ROS which may reactivate PKC. In the future, ROS will be validated as the promising therapeutic targets for prevention of tumor metastasis.