TY - JOUR
T1 - Mitosis perturbation by MASTL depletion impairs the viability of thyroid tumor cells
AU - Cetti, Elena
AU - Di Marco, Tiziana
AU - Mauro, Giuseppe
AU - Mazzoni, Mara
AU - Lecis, Daniele
AU - Minna, Emanuela
AU - Gioiosa, Lucia
AU - Brich, Silvia
AU - Pagliardini, Sonia
AU - Borrello, Maria Grazia
AU - Pruneri, Giancarlo
AU - Anania, Maria Chiara
AU - Greco, Angela
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - MASTL
KW - Mitotic catastrophe
KW - Non-oncogene addiction
KW - Target validation
KW - Thyroid tumor cells
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U2 - 10.1016/j.canlet.2018.11.010
DO - 10.1016/j.canlet.2018.11.010
M3 - Article
C2 - 30445205
AN - SCOPUS:85056830130
VL - 442
SP - 362
EP - 372
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
ER -