Abstract B120: Maternal embryonic leucine zipper kinase(MELK) induces invasion and migration of glioblastoma

Abstract

Abstract Maternal Embryonic Leucine Zipper Kinase(MELK) induces invasion and migration of glioblastoma Glioblastoma multiforme (GBM) is the most common cancer of the primary malignant brain tumors and one of the most difficult tumors to treat effectively. This tumor arises from star-shaped glial cells called “astrocytes.” Maternal embryonic leucine zipper kinase (MELK) is a member of the snf1/AMPK family of serin-threonine kinase which is cell cycle-dependent protein kinase. Although several members of the family are known to play roles in cell survival under metabolically challenging condition, the exact function of MELK has not previously been identified. MELK has recently emerged as an important gene in the field of cancer research. Several studies have reported that MELK level is dramatically increased in cancer tissues and it possibly contributes to cancer development. The several proteins such as ZPR9, NIPP1, and Cdc25B are reported the substrates of MELK, so far, but the significance of their phosphorylation is not clear. To identify the role of MELK in malignancy of GBM, we introduced the drug-induced transgene expression system to U87MG cell line by using the tetracycline(Tet)-inducible gene expression systems. To elucidate the MELK signaling pathway in brain cancer cells, we conducted human phospho-kinase array, 2D-PAGE and mass spectrometric analysis. We identified the vimentin as a downstream factor of MELK, and confirmed the expression of this target by artificial increased MELK. Vimentin, the intermediate filament protein, is reported as an important marker of Epithelial-to-mesenchymal transition (EMT) and a requisite regulator of mesenchymal cell migration. EMT is a critical event in the induction of cell motility and increased survival both under physiological situations like wound healing and during development as well as in malignant cells undergoing invasion and metastasis. Vimentin is characteristically upregulated in tumor cells undergoing EMT. Here, we show that MELK is necessary for the vimentin function in vitro, influencing their ability to cell migration. The data strongly support the hypothesis that MELK, unlike other family members, functions by regulating migration and invasion for tumor cell EMT induction rather than the cell cycle through regulation of vimentin. Citation Format: Sang-Un Choi, KwangRok Kim, Hyo Zin Cheon, Yoo Hwa Shon. Maternal embryonic leucine zipper kinase(MELK) induces invasion and migration of glioblastoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B120.