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
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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