Cellular and Molecular Biology



The signaling network of tumor invasion

G.K. Wang and W. Zhang

Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Offprint requests to: Wei Zhang, Ph.D., Department of Pathology, Unit 85, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030. Tel/Fax: 713-745-1103/713-792-5549. e-mail: wzhang@mdanderson.org

Summary. The ability of a cell to invade its surroundings is an important hallmark of malignant tumors and results from aberrant cell signaling mechanisms. The signal transduction that leads to tumor invasion can be broken down into major pathways. Even though the pathway systems are distinct in themselves, none of these pathways operate independently when it comes to transmitting signals that culminate in an invasive phenotype. That is, the malignant change in one receptor not only leads to malignant changes directly downstream but can also affect the molecules of many other pathways. Three major pathway systems involved in tumor invasion are discussed in this review: the integrin system, the insulin-like growth factor system, and the Rho family GTPases. Here we see that although the individual signaling systems can each contribute to invasion, each system is networked to others and should not be considered isolated. Each system is first reviewed as independent contributors to an invasive phenotype and then discussed in the context of interacting pathways that collectively result in tumor invasion. Histol Histopathol 20, 593-602 (2005).

Key words: Tumor invasion, Integrin, IGFPB, Rho, Crosstalk