ErbB-2 signals through Plexin-B1 to promote breast cancer metastasis
| Autor: | Thomas Worzfeld, Stefan Offermanns, Jakub M. Swiercz, Beate K. Straub, Kishor K. Sivaraj, Mario Looso |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
rho GTP-Binding Proteins CA15-3 Oncology medicine.medical_specialty Lung Neoplasms animal structures Receptor ErbB-2 RhoC Breast Neoplasms Nerve Tissue Proteins Receptors Cell Surface Biology Metastasis Mice Breast cancer ErbB Cell Line Tumor Internal medicine medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis Phosphorylation skin and connective tissue diseases Ovarian Neoplasms Mammary Neoplasms Experimental Cancer General Medicine Genes erbB-2 Prognosis medicine.disease Metastatic breast cancer Neoplasm Proteins Enzyme Activation Gene Expression Regulation Neoplastic HEK293 Cells Cancer cell Disease Progression Cancer research biology.protein Female Protein Processing Post-Translational Signal Transduction Research Article |
| Zdroj: | Journal of Clinical Investigation. 122:1296-1305 |
| ISSN: | 0021-9738 |
| Popis: | Diagnosis of metastatic breast cancer is associated with a very poor prognosis. New therapeutic targets are urgently needed, but their development is hampered by a lack of understanding of the mechanisms leading to tumor metastasis. Exemplifying this is the fact that the approximately 30% of all breast cancers overexpressing the receptor tyrosine kinase ErbB-2 are characterized by high metastatic potential and poor prognosis, but the signaling events downstream of ErbB-2 that drive cancer cell invasion and metastasis remain incompletely understood. Here we show that overexpression of ErbB-2 in human breast cancer cell lines leads to phosphorylation and activation of the semaphorin receptor Plexin-B1. This was required for ErbB-2–dependent activation of the pro-metastatic small GTPases RhoA and RhoC and promoted invasive behavior of human breast cancer cells. In a mouse model of ErbB-2–overexpressing breast cancer, ablation of the gene encoding Plexin-B1 strongly reduced the occurrence of metastases. Moreover, in human patients with ErbB-2–overexpressing breast cancer, low levels of Plexin-B1 expression correlated with good prognosis. Our data suggest that Plexin-B1 represents a new candidate therapeutic target for treating patients with ErbB-2–positive breast cancer. |
| Databáze: | OpenAIRE |
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