Mitosis perturbation by MASTL depletion impairs the viability of thyroid tumor cells
2019
Abstract Even if
thyroid tumorsare 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 functionalscreening, 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 tumorcells. 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 tumorcells to cisplatin. Our results demonstrate that MASTL represents vulnerability for
thyroid tumorcells, which could be explored as a therapeutic target for
thyroid cancer.
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