Oncotarget

Research Papers:

Mastl kinase, a promising therapeutic target, promotes cancer recurrence

Ling Wang _, Vivian Q. Luong, Peter J. Giannini and Aimin Peng

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2014; 5:11479-11489. https://doi.org/10.18632/oncotarget.2565

Metrics: PDF 2092 views  |   HTML 1988 views  |   ?  


Abstract

Ling Wang1, Vivian Q. Luong1, Peter J. Giannini1, Aimin Peng1

1Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583

Correspondence to:

Aimin Peng, e-mail: aimin.peng@unmc.edu

Keywords: cancer, chemotherapy, recurrence, Mastl, Greatwall

Received: June 16, 2014     Accepted: October 03, 2014     Published: December 22, 2014

ABSTRACT

Mastl kinase promotes mitotic progression and cell cycle reentry after DNA damage. We report here that Mastl is frequently upregulated in various types of cancer. This upregulation was correlated with cancer progression in breast and oral cancer, poor patient survival in breast cancer, and tumor recurrence in head and neck squamous cell carcinoma. We further investigated the role of Mastl in tumor resistance using cell lines derived from the initial and recurrent tumors of the same head and neck squamous cell carcinoma patients. Ectopic expression of Mastl in the initial tumor cells strongly promoted cell proliferation in the presence of cisplatin by attenuating DNA damage signaling and cell death. Mastl knockdown in recurrent tumor cells re-sensitized their response to cancer therapy in vitro and in vivo. Finally, Mastl targeting specifically potentiated cancer cells to cell death in chemotherapy while sparing normal cells. Thus, this study revealed that Mastl upregulation is involved in cancer progression and tumor recurrence after initial cancer therapy, and validated Mastl as a promising target to increase the therapeutic window.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 2565