Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression
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 bi...
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| Veröffentlicht in: | Cancer cell 2009-06, Vol.15 (6), p.477-488 |
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| creator | Reuter, Jason A. Ortiz-Urda, Susana Kretz, Markus Garcia, John Scholl, Florence A. Pasmooij, Anna M.G. Cassarino, David Chang, Howard Y. Khavari, Paul A. |
| description | 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 β1 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. |
| doi_str_mv | 10.1016/j.ccr.2009.04.002 |
| format | Article |
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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 β1 integrin subunit, disrupted network gene expression and attenuated tumorigenesis in vivo. 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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.</description><subject>Animals</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Line</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>CELLCYCLE</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelial Cells - physiology</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Humans</subject><subject>Integrin beta1 - metabolism</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Models, Biological</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Transplantation</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Protein Interaction Mapping</subject><subject>Signal Transduction</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Stromal Cells - pathology</subject><subject>Stromal Cells - physiology</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAQjRCIlsIP4IJ84pbUduw4ERISWhW6Uj84lLPl2JPFi9debGdpT_x1vNpVCxdOM5p5783Hq6q3BDcEk-583WgdG4rx0GDWYEyfVaekF33ddn33vOS85XVHcH9SvUppjQuHiOFldUIGJgSj4rT6fR0MOOtXaOnNrO3oAF3OG-XRnU1pBnQDYetUsgotDfhsJwsJlfbFfY5Kg3OzUxFdqxztfdHIUKrZBl-I-VeIP0ptF9wODLIeLZTXENHXGFYRUiqw19WLSbkEb47xrPr2-eJucVlf3X5ZLj5d1ZqzLtcgMOfd0NOBYFoSrftJCcEHQ4gauRhbNVFsDCUTp6QVyhjTMWCMDWaEvm_Pqo8H3e08bsDockpUTm6j3aj4IIOy8t-Ot9_lKuxkiznmTBSB90eBGH7OkLLc2LS_X3kIc5IUd4TTlhcgOQB1DClFmB6HECz3tsm1LLbJvW0SM1lsK5x3f2_3xDj6VAAfDgAoP9pZiDJpC-WZxkbQWZpg_yP_B3fEq8Y</recordid><startdate>20090602</startdate><enddate>20090602</enddate><creator>Reuter, Jason A.</creator><creator>Ortiz-Urda, Susana</creator><creator>Kretz, Markus</creator><creator>Garcia, John</creator><creator>Scholl, Florence A.</creator><creator>Pasmooij, Anna M.G.</creator><creator>Cassarino, David</creator><creator>Chang, Howard Y.</creator><creator>Khavari, Paul A.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20090602</creationdate><title>Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression</title><author>Reuter, Jason A. ; 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| subjects | Animals Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Line Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology CELLCYCLE Epithelial Cells - pathology Epithelial Cells - physiology Extracellular Matrix - metabolism Female Gene Expression Regulation, Neoplastic - physiology Humans Integrin beta1 - metabolism Mice Mice, SCID Models, Biological Neoplasm Invasiveness Neoplasm Transplantation Oligonucleotide Array Sequence Analysis Protein Interaction Mapping Signal Transduction Skin Neoplasms - metabolism Skin Neoplasms - pathology Stromal Cells - pathology Stromal Cells - physiology |
| title | Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression |
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