Disruption of Tumor Cell Adhesion Promotes Angiogenic Switch and Progression to Micrometastasis in RAF-Driven Murine Lung Cancer
Autor: | Esther Asan, Semra Ceteci, Christiaan Karreman, Fatih Ceteci, Boris W Kramer, Rudolf Götz, Ulf R. Rapp |
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Rok vydání: | 2007 |
Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Lung Neoplasms Angiogenic Switch Fluorescent Antibody Technique Apoptosis CELLCYCLE CDH1 Metastasis Mice Carcinoma Non-Small-Cell Lung Luciferases Cells Cultured beta Catenin Genes Dominant Mice Knockout Neovascularization Pathologic Reverse Transcriptase Polymerase Chain Reaction Endoderm Micrometastasis Adherens Junctions Cadherins Oncology SIGNALING Disease Progression Signal Transduction Adenoma Immunoblotting Mice Transgenic Adenocarcinoma Biology Adherens junction Antigens CD Cell Adhesion In Situ Nick-End Labeling medicine Animals Immunoprecipitation Neoplasm Invasiveness RNA Messenger Cell adhesion Lung cancer Cancer Cell Biology medicine.disease Proto-Oncogene Proteins c-raf Cancer research biology.protein Endothelium Vascular Biomarkers |
Zdroj: | Cancer Cell. 12:145-159 |
ISSN: | 1535-6108 |
Popis: | SummaryProgression of non-small-cell lung cancer (NSCLC) to metastasis is poorly understood. Two genetic approaches were used to evaluate the role of adherens junctions in a C-RAF driven mouse model for NSCLC: conditional ablation of the cdh1 gene and expression of dominant-negative (dn) E-cadherin. Disruption of E-cadherin caused massive formation of intratumoral vessels that was reversible in the early phase of induction. Vascularized tumors grew more rapidly, developed invasive fronts, and gave rise to micrometastasis. β-catenin was identified as a critical effector of E-cadherin disruption leading to upregulation of VEGF-A and VEGF-C. In vivo, lung tumor cells with disrupted E-cadherin expressed β-catenin target genes normally found in other endodermal lineages suggesting that reprogramming may be involved in metastatic progression. |
Databáze: | OpenAIRE |
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