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Open AccessArticle

CITK Loss Inhibits Growth of Group 3 and Group 4 Medulloblastoma Cells and Sensitizes Them to DNA-Damaging Agents

1
Neuroscience Institute Cavalieri Ottolenghi, 10043 Turin, Italy
2
Department of Neurosciences, University of Turin, 10126 Turin, Italy
3
Neuroscience Institute of Turin (NIT), 10043 Turin, Italy
4
Department of Radiology, San Luigi Gonzaga Hospital, University of Turin, 10043 Turin, Italy
5
Radiation Oncology, Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, 10043 Turin, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(3), 542; https://doi.org/10.3390/cancers12030542
Received: 10 February 2020 / Revised: 15 February 2020 / Accepted: 23 February 2020 / Published: 26 February 2020
(This article belongs to the Special Issue Pediatric Brain Tumor)
Medulloblastoma (MB) is the most common malignant brain tumor in children, and it is classified into four biological subgroups: WNT, Sonic Hedgehog (SHH), Group 3 and Group 4. The current treatment is surgery, followed by irradiation and chemotherapy. Unfortunately, these therapies are only partially effective. Citron kinase protein (CITK) has been proposed as a promising target for SHH MB, whose inactivation leads to DNA damage and apoptosis. D283 and D341 cell lines (Group 3/Group 4 MB) were silenced with established siRNA sequences against CITK, to assess the direct effects of its loss. Next, D283, D341, ONS-76 and DAOY cells were treated with ionizing radiation (IR) or cisplatin in combination with CITK knockdown. CITK depletion impaired proliferation and induced cytokinesis failure and apoptosis of G3/G4 MB cell lines. Furthermore, CITK knockdown produced an accumulation of DNA damage, with reduced RAD51 nuclear levels. Association of IR or cisplatin with CITK depletion strongly impaired the growth potential of all tested MB cells. These results indicate that CITK inactivation could prevent the expansion of G3/G4 MB and increase their sensitivity to DNA-damaging agents, by impairing homologous recombination. We suggest that CITK inhibition could be broadly associated with IR and adjuvant therapy in MB treatment. View Full-Text
Keywords: medulloblastoma; radiation; cisplatin; TP53; 53BP1; genomic instability; double strand break; DBS; HR medulloblastoma; radiation; cisplatin; TP53; 53BP1; genomic instability; double strand break; DBS; HR
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MDPI and ACS Style

Pallavicini, G.; Iegiani, G.; Berto, G.E.; Calamia, E.; Trevisiol, E.; Veltri, A.; Allis, S.; Di Cunto, F. CITK Loss Inhibits Growth of Group 3 and Group 4 Medulloblastoma Cells and Sensitizes Them to DNA-Damaging Agents. Cancers 2020, 12, 542.

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