Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer

Abstract

Introduction Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active genedependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel-BiskisReilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK).

Cortical localization of Maternal Embryonic Leucine zipper Kinase (MELK) implicated in cytokinesis in early Xenopus embryos

“…12,15 Moreover, high levels of MELK were also associated with poor prognosis in breast cancer. 16 Thus MELK appears also to be an important prognosis marker for some cancers.…”

The structures of the kinase domain and UBA domain of MPK38 suggest the activation mechanism for kinase activity

“…Overexpression and hyperactivation of MELK are involved in initiation of the cell cycle but are barely detectable during cell differentiation (Badouel et al, 2010). Recent research shows that MELK expression is correlated with malignancy in a broad spectrum of cancers (Gray et al, 2005;Marie et al, 2008;Nakano et al, 2008;Pickard et al, 2009;Ku et al, 2010). Overexpression of MELK is associated with a poor prognosis in breast cancer and glioblastoma patients.…”

“…Overexpression of MELK is associated with a poor prognosis in breast cancer and glioblastoma patients. MELK is hyperactivated in cell lines derived from a colorectal carcinoma (Pickard et al, 2009;Nakano et al, 2008;Ku et al, 2010). MELK plays a critical role in the formation or maintenance of cancer stem cells (Sutter et al, 2007;Hebbard et al, 2010).…”

MELK (maternal embryonic leucine zipper kinase)

“…Note MELK expression was found significantly upregulated in the breast cancers (Pickard et al, 2009). Prognosis MELK expression is associated with poor patient survival.…”