| First Author | Wada M | Year | 2017 |
| Journal | Oncogene | Volume | 36 |
| Issue | 47 | Pages | 6649-6657 |
| PubMed ID | 28783172 | Mgi Jnum | J:251097 |
| Mgi Id | MGI:6101025 | Doi | 10.1038/onc.2017.274 |
| Citation | Wada M, et al. (2017) P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment. Oncogene 36(47):6649-6657 |
| abstractText | The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38delta) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38delta is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38delta (PyMT/p38delta(-/-)) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38delta in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38delta also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38delta in the human breast cell lines. These studies define a previously unappreciated role for p38delta in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38delta protein as a key factor in breast cancer. Lack of p38delta resulted in reduced primary tumor size and blocked the metastatic potential to the lungs. |
