| First Author | Wang Y | Year | 2014 |
| Journal | Elife | Volume | 3 |
| Pages | e01763 | PubMed ID | 24844244 |
| Mgi Jnum | J:228548 | Mgi Id | MGI:5707573 |
| Doi | 10.7554/eLife.01763 | Citation | Wang Y, et al. (2014) MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife 3:e01763 |
| abstractText | Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC. Ablation of MELK selectively impairs proliferation of basal-like, but not luminal breast cancer cells both in vitro and in vivo. Mechanistically, depletion of MELK in BBC cells induces caspase-dependent cell death, preceded by defective mitosis. Finally, we find that Melk is not required for mouse development and physiology. Together, these data indicate that MELK is a normally non-essential kinase, but is critical for BBC and thus represents a promising selective therapeutic target for the most aggressive subtype of breast cancer.DOI: http://dx.doi.org/10.7554/eLife.01763.001. |
