A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells

Yubao Wang; Ben B Li; Jing Li; Thomas M Roberts; Jean J Zhao

doi:10.1016/j.isci.2018.10.015

A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells

iScience. 2018 Nov 30:9:149-160. doi: 10.1016/j.isci.2018.10.015. Epub 2018 Oct 18.

Authors

Yubao Wang¹, Ben B Li², Jing Li³, Thomas M Roberts⁴, Jean J Zhao⁵

Affiliations

¹ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yubao_wang@dfci.harvard.edu.
² Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
⁴ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
⁵ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: jean_zhao@dfci.harvard.edu.

Abstract

The role of maternal and embryonic leucine zipper kinase (MELK) in cancer cell proliferation has been contentious, with recent studies arriving at disparate conclusions. We investigated the in vitro dependency of cancer cells on MELK under a range of assay conditions. Abrogation of MELK expression has little effect under common culture conditions, in which cells are seeded at high densities and reach confluence in 3-5 days. However, MELK dependency becomes clearly apparent in clonogenic growth assays using either RNAi or CRISPR technologies to modulate MELK expression. This dependency is in sharp contrast to that of essential genes, such as those encoding classic mitotic kinases, but is similar to that of other oncogenes including MYC and KRAS. Our study provides an example demonstrating some of the challenges encountered in cancer target validation, and reveals how subtle, but important, technical variations can ultimately lead to divergent outcomes and conclusions.

Keywords: Cancer; Technical Aspects of Cell Biology; Techniques in Genetics.

Abstract

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