Abstract 75: Identification and characterization of novel MELK (maternal embryonic leucine zipper kinase) substrates in breast cancer cells

Abstract

Abstract Breast cancer is the most common malignancy among women worldwide. Treatment for breast cancer acting on molecular targets in critical signaling pathways in cancer cells have successfully reduced the motility rate in a subset of breast cancer patients, but a significant portion of patients cannot expect to have benefits from these treatments. Therefore, development of new therapeutics for those patients urgently required. Toward the goal of cancer-specific drug development, we previously identified MELK (maternal embryonic leucine zipper kinase) as a target for development of novel breast cancer therapy through genome-wide expression profile analysis. MELK was over-expressed in the great majority of breast cancer cells, particularly in TN breast cancer cells, and knockdown of MELK significantly suppressed the growth of breast cancer cells. Concordantly, the cells, which were transiently induced MELK, promoted its proliferation. Furthermore, cells in which over-expression of MELK were likely to increase the proportion of breast cancer-initiating stem cells more than those transfected with mock vector or kinase-dead MELK mutant plasmid. Although several substrates of MELK were reported, we are still not fully understood how MELK contributes to breast cancer development or progression. To elucidate the MELK signaling pathway in breast cancer cells, we examined 2D-PAGE and mass spectrometric analysis. Finally, we successfully identified two novel substrates of MELK. We confirmed the phosphorylation of these substrates by MELK via in vitro kinase assay and identified phosphorylation sites on each substrate by mass spectrometry. These results provide new information for better understanding of the biological role of MELK. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 75. doi:1538-7445.AM2012-75