RRC ID 54727
Author Cetti E, Di Marco T, Mauro G, Mazzoni M, Lecis D, Minna E, Gioiosa L, Brich S, Pagliardini S, Borrello MG, Pruneri G, Anania MC, Greco A.
Title Mitosis perturbation by MASTL depletion impairs the viability of thyroid tumor cells.
Journal Cancer Lett
Abstract Even if thyroid tumors are generally curable, a fraction will develop resistance to therapy and progress towards undifferentiated forms, whose treatment remains a demanding challenge. To identify potential novel targets for treatment of thyroid cancer, in a previous study using siRNA-mediated functional screening, we identified several genes that are essential for the growth of thyroid tumor, but not normal cells. Among the top-ranking hits, we found microtubule associated serine/threonine kinase-like (MASTL), which is known to play an essential role in mitosis regulation, and is also involved in the DNA damage response. Herein, we examine the effects of MASTL depletion on growth and viability of thyroid tumor cells. MASTL depletion impaired cell proliferation and increased the percentage of cells presenting nuclear anomalies, which are indicative of mitotic catastrophe. Furthermore, MASTL depletion was associated with enhanced DNA damage. All these effects eventually led to cell death, characterized by the presence of apoptotic markers. Moreover, MASTL depletion sensitized thyroid tumor cells to cisplatin. Our results demonstrate that MASTL represents vulnerability for thyroid tumor cells, which could be explored as a therapeutic target for thyroid cancer.
Volume 442
Pages 362-372
Published 2019-2-1
DOI 10.1016/j.canlet.2018.11.010
PII S0304-3835(18)30674-8
PMID 30445205
MeSH Antineoplastic Agents / pharmacology* Apoptosis Apoptosis Regulatory Proteins / metabolism Cell Line, Tumor Cell Proliferation Cell Survival Cisplatin / pharmacology* Histones / metabolism Humans Microtubule-Associated Proteins / deficiency* Microtubule-Associated Proteins / genetics Mitosis* / drug effects Protein Serine-Threonine Kinases / deficiency* Protein Serine-Threonine Kinases / genetics Signal Transduction Thyroid Neoplasms / drug therapy Thyroid Neoplasms / enzymology* Thyroid Neoplasms / genetics Thyroid Neoplasms / pathology
IF 6.508
Times Cited 3
Human and Animal Cells HTC/C3(RCB0452)