MUC1 drives c-Met-dependent migration and scattering
| Autor: | Derrick Broka, Benjamin G. Bitler, Joyce A. Schroeder, Jeanne M. V. Louderbough, Teresa M. Horm |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
C-Met Transcription Genetic Down-Regulation Breast Neoplasms Tumor initiation Biology Article Metastasis chemistry.chemical_compound Epidermal growth factor Cell Movement Cell Line Tumor medicine Humans Neoplasm Metastasis skin and connective tissue diseases Molecular Biology MUC1 Epidermal Growth Factor Cell growth Mucin-1 Proto-Oncogene Proteins c-met medicine.disease ErbB Receptors Oncology chemistry Cancer research Disease Progression Female Peptides Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecular cancer research : MCR. 10(12) |
| ISSN: | 1557-3125 |
| Popis: | The transmembrane mucin MUC1 is overexpressed in most ductal carcinomas, and its overexpression is frequently associated with metastatic progression. MUC1 can drive tumor initiation and progression via interactions with many oncogenic partners, including β-catenin, the EGF receptor (EGFR) and Src. The decoy peptide protein transduction domain MUC1 inhibitory peptide (PMIP) has been shown to inhibit the tumor promoting activities of MUC1 in breast and lung cancer, including cell growth and invasion, and its usage suppresses metastatic progression in mouse models of breast cancer. To further characterize the reduced metastasis observed upon PMIP treatment, we conducted motility assays and observed that PMIP inhibits cell motility of breast cancer cells. To determine the mechanism by which PMIP inhibits motility, we evaluated changes in global gene transcription upon PMIP treatment, and identified a number of genes with altered expression in response to PMIP. Among these genes is the metastatic mediator, c-Met, a transmembrane tyrosine kinase that can promote cell scattering, migration, and invasion. To further investigate the role of c-Met in MUC1-dependent metastatic events, we evaluated the effects of MUC1 expression and EGFR activation on breast cancer cell scattering, branching, and migration. We found that MUC1 strongly promoted all of these events and this effect was further amplified by EGF treatment. Importantly, the effect of MUC1 and EGF on these phenotypes was dependent upon c-Met activity. Overall, these results indicate that PMIP can block the expression of a key metastatic mediator, further advancing its potential use as a clinical therapeutic. Mol Cancer Res; 10(12); 1544–54. ©2012 AACR. |
| Databáze: | OpenAIRE |
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