PDZ and LIM domain protein 2 (PDLIM2) is connected to epithelial-to-mesenchymal transition in breast cancer
| Autoři | |
|---|---|
| Rok publikování | 2017 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | PDZ and LIM domain protein 2 (PDLIM2), a member of the ALP protein family, is a cytoskeletal and nuclear protein that regulates the activity of several transcription factors, e.g., NF-kappaB and STAT. Its deregulation was observed in several malignancies. PDLIM2 expression was shown epigenetically repressed by promoter hypermetylation in different cancers, nonetheless, PDLIM2 is also highly expressed in invasive cancer: we recently identified PDLIM2 as a protein associated with lymph node metastasis in luminal A breast cancer. Here we aimed to unravel these contradictory mechanisms in breast cancer models. First, we studied and confirmed a promoting role of PDLIM2 in epithelial-to-mesenchymal transition (EMT) in MCF7 cells, a model of luminal A tumors, which was accompanied by increased cell rigidity. However, in MCF10A cells, a model of normal breast epithelium, PDLIM2 helped to maintain epithelial phenotype. Furthermore, exposition of MCF7 cells to hypoxic conditions was able to increase PDLIM2 protein levels, but no such effect was observed in MCF10A cells. Likewise, PDLIM2 overexpression significantly increased cell migration, invasion, and proliferation in MCF7 cells but decreased proliferation and increased adhesion in MCF10A cells. These data indicate a context dependent role of PDLIM2 which may play a tumour suppressor role in early phase of tumour development but oncoprotein role in later phase of tumorigenesis. Our latest data from in vivo mice model further support this hypothesis. |
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