MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells
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CitationWang, Y., Y. Lee, L. Baitsch, A. Huang, Y. Xiang, H. Tong, A. Lako, et al. 2014. “MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells.” eLife 3 (1): e01763. doi:10.7554/eLife.01763. http://dx.doi.org/10.7554/eLife.01763.
AbstractDespite 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
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