Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression CANCER CELL Reuter, J. A., Ortiz-Urda, S., Kretz, M., Garcia, J., Scholl, F. A., Pasmooij, A. M., Cassarino, D., Chang, H. Y., Khavari, P. A. 2009; 15 (6): 477-488


To elucidate mechanisms of cancer progression, we generated inducible human neoplasia in three-dimensionally intact epithelial tissue. Gene expression profiling of both epithelia and stroma at specific time points during tumor progression revealed sequential enrichment of genes mediating discrete biologic functions in each tissue compartment. A core cancer progression signature was distilled using the increased signaling specificity of downstream oncogene effectors and subjected to network modeling. Network topology predicted that tumor development depends on specific extracellular matrix-interacting network hubs. Blockade of one such hub, the beta1 integrin subunit, disrupted network gene expression and attenuated tumorigenesis in vivo. Thus, integrating network modeling and temporal gene expression analysis of inducible human neoplasia provides an approach to prioritize and characterize genes functioning in cancer progression.

View details for DOI 10.1016/j.ccr.2009.04.002

View details for Web of Science ID 000266686500006

View details for PubMedID 19477427

View details for PubMedCentralID PMC3050547