MELK-a conserved kinase: functions, signaling, cancer, and controversy.

Ranjit Ganguly,Ahmed Mohyeldin,Ichiro Nakano,Monique Beullens,Jordyn Thiel,Harley I Kornblum

doi:10.1186/s40169-014-0045-y

Abstract

Maternal embryonic leucine zipper kinase (MELK) is a highly conserved serine/threonine kinase initially found to be expressed in a wide range of early embryonic cellular stages, and as a result has been implicated in embryogenesis and cell cycle control. Recent evidence has identified a broader spectrum of tissue expression pattern for this kinase than previously appreciated. MELK is expressed in several human cancers and stem cell populations. Unique spatial and temporal patterns of expression within these tissues suggest that MELK plays a prominent role in cell cycle control, cell proliferation, apoptosis, cell migration, cell renewal, embryogenesis, oncogenesis, and cancer treatment resistance and recurrence. These findings have important implications for our understanding of development, disease, and cancer therapeutics. Furthermore understanding MELK signaling may elucidate an added dimension of stem cell control.

Highlights

As a member of the AMPK/Snf1 family, Maternal Embryonic Leucine-zipper Kinase (MELK) encodes a serine/ threonine kinase that is highly conserved across a variety of mammalian and non-mammalian species
In breast cancer models Lin et al showed that the effect of MELK on cancer cell growth is associated with resistance to apoptosis through the inhibition of a proapoptotic function of Bcl-G [23], these results are challenged by other studies [24]
MELK knockdown decreased proliferation and anchorage-independent growth in vitro, and decreased tumor growth in vivo in breast, pancreatic, and colorectal carcinomas [29]. These findings suggest that MELK activity is implicated in tumor growth and aggressiveness, and inhibition of MELK may be an attractive cancer therapeutic target

Summary

Introduction

As a member of the AMPK/Snf1 family, Maternal Embryonic Leucine-zipper Kinase (MELK) encodes a serine/ threonine kinase that is highly conserved across a variety of mammalian and non-mammalian species. We have a better understanding of some basic mechanisms, functions, and signaling pathways involving MELK, including interactions that link it with tumor progression. In non-mammalian systems such as Caenorhabditis elegans, Danio rerio (zebra fish), and Xenopus, MELK plays an important role in cell division, as well as propagation and maintenance of some organ-specific stem cells [12,13,14].

Results

Conclusion