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

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

Summary: 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 exp...

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Main Authors: Yubao Wang, Ben B. Li, Jing Li, Thomas M. Roberts, Jean J. Zhao
Format: Article
Language:English
Published: Elsevier 2018-11-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004218301743
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spelling doaj-7f6127a3823e4261a6df4a5ee57be8d02020-11-25T00:11:43ZengElsevieriScience2589-00422018-11-019149160A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer CellsYubao Wang0Ben B. Li1Jing Li2Thomas M. Roberts3Jean J. Zhao4Department 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; Corresponding authorDepartment 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, USADepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USADepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USADepartment 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; Corresponding authorSummary: 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. : Techniques in Genetics; Technical Aspects of Cell Biology; Cancer Subject Areas: Techniques in Genetics, Technical Aspects of Cell Biology, Cancerhttp://www.sciencedirect.com/science/article/pii/S2589004218301743
collection DOAJ
language English
format Article
sources DOAJ
author Yubao Wang
Ben B. Li
Jing Li
Thomas M. Roberts
Jean J. Zhao
spellingShingle Yubao Wang
Ben B. Li
Jing Li
Thomas M. Roberts
Jean J. Zhao
A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells
iScience
author_facet Yubao Wang
Ben B. Li
Jing Li
Thomas M. Roberts
Jean J. Zhao
author_sort Yubao Wang
title A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells
title_short A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells
title_full A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells
title_fullStr A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells
title_full_unstemmed A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells
title_sort conditional dependency on melk for the proliferation of triple-negative breast cancer cells
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2018-11-01
description Summary: 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. : Techniques in Genetics; Technical Aspects of Cell Biology; Cancer Subject Areas: Techniques in Genetics, Technical Aspects of Cell Biology, Cancer
url http://www.sciencedirect.com/science/article/pii/S2589004218301743
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