Exploration of Alternative Approaches to Citron Kinase Inhibition for Glioblastoma Treatment
4 affiliations
- 1Neuroscience Institute Cavalieri Ottolenghi, 10043 Orbassano, Italy
- 2Department of Neuroscience “Rita Levi Montalcini”, University of Turin, 10126 Turin, Italy
- 3INOC—Istituto Nazionale Oncologico Candiolo, IRCCS, 10060 Candiolo, Italy
- 4Department of Oncology, University of Turin, 10043 Turin, Italy
Abstract
Glioblastoma (GBM) remains a highly aggressive brain tumor with limited therapeutic options, highlighting the need to identify novel tumor vulnerabilities. Citron kinase (CITK), a protein involved in cytokinesis and genome stability, is required for the proliferation and survival of neural progenitors and has previously emerged as a potential therapeutic target in medulloblastoma (MB). Here, we investigated the effects of CITK depletion and pharmacological inhibition in two patient-derived GBM stem cell models. CITK was depleted by siRNA or pharmacologically targeted using the first selective kinase inhibitor so far described, C3TD879 (c879). We also explored the polypharmacological inhibitor Lestaurtinib. Effects on spheroid growth, cytokinesis, cytotoxicity, DNA damage-associated proteins, apoptotic markers, and cell-cycle regulators were assessed. CITK depletion partially impaired spheroid growth, slightly increased multinucleation, and led to cytotoxicity in both GBM models, while effects on DNA damage-associated proteins were cell-line dependent. Selective CITK inhibition with c879 slightly reduced spheroid growth and only partially recapitulated the cellular and molecular effects of CITK depletion. Lestaurtinib produced stronger spheroid growth inhibition and cytokinesis defects, while inducing limited cytotoxicity and heterogeneous molecular responses. In summary, the tested GBM models were shown to be moderately sensitive to CITK depletion and selective catalytic inhibition, while Lestaurtinib showed the strongest effects, which mimicked only in part the effects of CITK loss.
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BibTeX
@article{ferraro2026exploration,
title = {{Exploration of Alternative Approaches to Citron Kinase Inhibition for Glioblastoma Treatment}},
author = {Alessia Ferraro and Letizia Lazzerini and Giorgia Iegiani and Francesca De Bacco and Carla Boccaccio and Ferdinando Di Cunto},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219678},
url = {https://www.mdpi.com/1422-0067/27/21/9678},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exploration of Alternative Approaches to Citron Kinase Inhibition for Glioblastoma Treatment
AU - Alessia Ferraro
AU - Letizia Lazzerini
AU - Giorgia Iegiani
AU - Francesca De Bacco
AU - Carla Boccaccio
AU - Ferdinando Di Cunto
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219678
UR - https://www.mdpi.com/1422-0067/27/21/9678
AB - Glioblastoma (GBM) remains a highly aggressive brain tumor with limited therapeutic options, highlighting the need to identify novel tumor vulnerabilities. Citron kinase (CITK), a protein involved in cytokinesis and genome stability, is required for the proliferation and survival of neural progenitors and has previously emerged as a potential therapeutic target in medulloblastoma (MB). Here, we investigated the effects of CITK depletion and pharmacological inhibition in two patient-derived GBM stem cell models. CITK was depleted by siRNA or pharmacologically targeted using the first selective kinase inhibitor so far described, C3TD879 (c879). We also explored the polypharmacological inhibitor Lestaurtinib. Effects on spheroid growth, cytokinesis, cytotoxicity, DNA damage-associated proteins, apoptotic markers, and cell-cycle regulators were assessed. CITK depletion partially impaired spheroid growth, slightly increased multinucleation, and led to cytotoxicity in both GBM models, while effects on DNA damage-associated proteins were cell-line dependent. Selective CITK inhibition with c879 slightly reduced spheroid growth and only partially recapitulated the cellular and molecular effects of CITK depletion. Lestaurtinib produced stronger spheroid growth inhibition and cytokinesis defects, while inducing limited cytotoxicity and heterogeneous molecular responses. In summary, the tested GBM models were shown to be moderately sensitive to CITK depletion and selective catalytic inhibition, while Lestaurtinib showed the strongest effects, which mimicked only in part the effects of CITK loss.
SN - 1422-0067
ER -