Research Paper Volume 14, Issue 17 pp 7093—7108
Tyrosine kinase receptor RON activates MAPK/RSK/CREB signal pathway to enhance CXCR4 expression and promote cell migration and invasion in bladder cancer
Figure 7. Proposed mechanistic scheme of RON promoting tumor invasion in bladder cancer. MSP stimulation induces RON dimerization by binding the sema domain, which stimulates the Erk1/2-RSK signal transduction pathway regulating RON-mediated activities such as cell growth and invasiveness. Activated ERK1 and ERK2 also stimulate RSK2 and promote RSK2 nuclear translocation, which induced CREB phosphorylation. Phospho-CREB binds cAMP-responsive element (CRE) site of CXCR4, thereby inducing its transcription and over-expression.