Priority Research Papers:

p53-independent p21 induction by MELK inhibition

Tatsuo Matsuda, Taigo Kato, Kazuma Kiyotani, Yunus Emre Tarhan, Vassiliki Saloura, Suyoun Chung, Koji Ueda, Yusuke Nakamura _ and Jae-Hyun Park

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:57938-57947. https://doi.org/10.18632/oncotarget.18488

Metrics: PDF 2127 views  |   HTML 5099 views  |   ?  


Tatsuo Matsuda1, Taigo Kato1, Kazuma Kiyotani1, Yunus Emre Tarhan1, Vassiliki Saloura1, Suyoun Chung2, Koji Ueda3, Yusuke Nakamura1,4 and Jae-Hyun Park1

1 Department of Medicine, The University of Chicago, Chicago, IL, USA

2 OncoTherapy Science Inc., Kawasaki, Japan

3 Project for Realization of Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan

4 Department of Surgery, The University of Chicago, Chicago, IL, USA

Correspondence to:

Yusuke Nakamura, email:

Keywords: maternal embryonic leucine zipper kinase, molecular target, p21, p53, FoxO family

Received: April 12, 2017 Accepted: June 01, 2017 Published: June 15, 2017


MELK play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness. Therefore, MELK is a promising therapeutic target for a wide range of cancers. Although p21 is a well-known p53-downstream gene, we found that treatment with a potent MELK inhibitor, OTS167, could induce p21 protein expression in cancer cell lines harboring loss-of-function TP53 mutations. We also confirmed that MELK knockdown by siRNA induced the p21 expression in p53-deficient cancer cell lines and caused the cell cycle arrest at G1 phase. Further analysis indicated that FOXO1 and FOXO3, two known transcriptional regulators of p21, were phosphorylated by MELK and thus be involved in the induction of p21 after MELK inhibition. Collectively, our herein findings suggest that MELK inhibition may be effective for human cancers even if TP53 is mutated.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 18488