Loss of the Par3 Polarity Protein Promotes Breast Tumorigenesis and Metastasis
| Autor: | Luke McCaffrey, JoAnne Montalbano, Constantina Mihai, Ian G. Macara |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Breast Neoplasms Cell Cycle Proteins MMP9 Biology medicine.disease_cause Article Metastasis Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Mice 0302 clinical medicine RNA interference Cell polarity medicine Tumor Cells Cultured Gene silencing Animals Humans Neoplasm Metastasis Phosphorylation Protein Kinase C 030304 developmental biology Adaptor Proteins Signal Transducing Cell Proliferation Regulation of gene expression 0303 health sciences Cell Polarity Mammary Neoplasms Experimental Membrane Proteins Cell Biology medicine.disease Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Matrix Metalloproteinase 9 Oncology 030220 oncology & carcinogenesis Cancer research Female RNA Interference Signal transduction Carcinogenesis Cell Adhesion Molecules |
| Zdroj: | Cancer Cell. 22(5):601-614 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2012.10.003 |
| Popis: | SummaryLoss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. To address this issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras61L expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer. |
| Databáze: | OpenAIRE |
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