SIAH ubiquitin ligases regulate breast cancer cell migration and invasion independent of the oxygen status
| Autor: | Carolyn Algire, Thomas G. Hofmann, Sonja Matt, Holger Hess-Stumpp, Andrea Haegebarth, Sven Christian, M Gordian Adam |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
SIAH ubiquitin ligases
p27Kip1 stathmin Ubiquitin-Protein Ligases Stathmin Apoptosis Breast Neoplasms SIAH1 Biology migration SIAH2 Microtubules Metastasis Breast cancer breast cancer Ubiquitin Cell Movement Report Cell Line Tumor medicine metastasis Humans Neoplasm Invasiveness Neoplasm Metastasis Molecular Biology seven-in-absentia Cell Proliferation Cell growth Cancer Nuclear Proteins Cell migration Cell Biology medicine.disease invasion Gene Knockdown Techniques Cancer cell Cancer research biology.protein MCF-7 Cells RNA Interference Cyclin-Dependent Kinase Inhibitor p27 Developmental Biology |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | Seven-in-absentia homolog (SIAH) proteins are evolutionary conserved RING type E3 ubiquitin ligases responsible for the degradation of key molecules regulating DNA damage response, hypoxic adaptation, apoptosis, angiogenesis, and cell proliferation. Many studies suggest a tumorigenic role for SIAH2. In breast cancer patients SIAH2 expression levels correlate with cancer aggressiveness and overall patient survival. In addition, SIAH inhibition reduced metastasis in melanoma. The role of SIAH1 in breast cancer is still ambiguous; both tumorigenic and tumor suppressive functions have been reported. Other studies categorized SIAH ligases as either pro- or antimigratory, while the significance for metastasis is largely unknown. Here, we re-evaluated the effects of SIAH1 and SIAH2 depletion in breast cancer cell lines, focusing on migration and invasion. We successfully knocked down SIAH1 and SIAH2 in several breast cancer cell lines. In luminal type MCF7 cells, this led to stabilization of the SIAH substrate Prolyl Hydroxylase Domain protein 3 (PHD3) and reduced Hypoxia-Inducible Factor 1α (HIF1α) protein levels. Both the knockdown of SIAH1 or SIAH2 led to increased apoptosis and reduced proliferation, with comparable effects. These results point to a tumor promoting role for SIAH1 in breast cancer similar to SIAH2. In addition, depletion of SIAH1 or SIAH2 also led to decreased cell migration and invasion in breast cancer cells. SIAH knockdown also controlled microtubule dynamics by markedly decreasing the protein levels of stathmin, most likely via p27Kip1. Collectively, these results suggest that both SIAH ligases promote a migratory cancer cell phenotype and could contribute to metastasis in breast cancer. |
| Databáze: | OpenAIRE |
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