CKAP2L Promotes Proliferation and Migration of Glioma Cells in a DIAPH3-Deficient Model
- 1College of Health and Life Sciences, Hamad Bin Khalifa University, Penrose House Building, Education City, Doha P.O. Box 34110, Qatar
- 2Developmental Neurobiology Laboratory, Institute of Neuroscience, Université Catholique de Louvain, 1200 Brussels, Belgium
Abstract
In humans, low expression of DIAPH3 is associated with poor prognosis in glioblastoma patients. In mice, DIAPH3 loss induces aberrant mitosis, chromosomal instability, and cell death; whereas the combined loss of DIAPH3 and p53 causes high-grade diffuse glioma and accelerates tumor onset. In this study, we used Diaph3/p53 double conditional knockout mice (dcKO) and ultra-high-resolution MRI to detect and characterize the development and progression of glioma. We transcriptionally profiled early and advanced gliomas and identified stage-dependent alterations in molecular signatures as the tumor progresses. Notably, genetic pathways underlying self-renewal and extracellular matrix (ECM) interactions were upregulated at the expense of neural activity signature, which was severely shrunk. CKAP2L was identified as a differentially expressed gene at both early and advanced tumor stages in the dcKO mice. A subsequent siRNA screen to identify genes involved in proliferation and migration of glioblastoma cells identified CKAP2L as a top hit. Functional studies showed that CKAP2L depletion reduced proliferation and migration and induced cell accumulation in G2/M phase of the cell cycle. We also used data mining and thoroughly characterized the relationship between CKAP2L expression and glioma development. We found that CKAP2L expression correlates with proliferative and progenitor-associated markers, pointing to a potential role in maintaining highly proliferative and progenitor-like tumor cell state. We also identified a differentially methylated CpG site in the CKAP2L promoter that was associated with changes in gene expression across glioma datasets. Overall, our findings show that CKAP2L may contribute to glioma progression, help distinguish tumor grade, and represent a potential therapeutic target in glioblastoma treatment.
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BibTeX
@article{mahdi2026ckap2l,
title = {{CKAP2L Promotes Proliferation and Migration of Glioma Cells in a DIAPH3-Deficient Model}},
author = {Asma Mahdi and Arwa Aldaalis and Georges Chehade and Eva On-Chai Lau and Hend Salah Fayed and Ayman Al Haj Zen and Mohamed Aittaleb and Maisa Ismael Alkailani and Fadel Tissir},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211996},
url = {https://www.mdpi.com/2073-4409/15/21/1996},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CKAP2L Promotes Proliferation and Migration of Glioma Cells in a DIAPH3-Deficient Model
AU - Asma Mahdi
AU - Arwa Aldaalis
AU - Georges Chehade
AU - Eva On-Chai Lau
AU - Hend Salah Fayed
AU - Ayman Al Haj Zen
AU - Mohamed Aittaleb
AU - Maisa Ismael Alkailani
AU - Fadel Tissir
PY - 2026
DA - 2026/10/31
JO - Cells
DO - 10.3390/cells15211996
UR - https://www.mdpi.com/2073-4409/15/21/1996
AB - In humans, low expression of DIAPH3 is associated with poor prognosis in glioblastoma patients. In mice, DIAPH3 loss induces aberrant mitosis, chromosomal instability, and cell death; whereas the combined loss of DIAPH3 and p53 causes high-grade diffuse glioma and accelerates tumor onset. In this study, we used Diaph3/p53 double conditional knockout mice (dcKO) and ultra-high-resolution MRI to detect and characterize the development and progression of glioma. We transcriptionally profiled early and advanced gliomas and identified stage-dependent alterations in molecular signatures as the tumor progresses. Notably, genetic pathways underlying self-renewal and extracellular matrix (ECM) interactions were upregulated at the expense of neural activity signature, which was severely shrunk. CKAP2L was identified as a differentially expressed gene at both early and advanced tumor stages in the dcKO mice. A subsequent siRNA screen to identify genes involved in proliferation and migration of glioblastoma cells identified CKAP2L as a top hit. Functional studies showed that CKAP2L depletion reduced proliferation and migration and induced cell accumulation in G2/M phase of the cell cycle. We also used data mining and thoroughly characterized the relationship between CKAP2L expression and glioma development. We found that CKAP2L expression correlates with proliferative and progenitor-associated markers, pointing to a potential role in maintaining highly proliferative and progenitor-like tumor cell state. We also identified a differentially methylated CpG site in the CKAP2L promoter that was associated with changes in gene expression across glioma datasets. Overall, our findings show that CKAP2L may contribute to glioma progression, help distinguish tumor grade, and represent a potential therapeutic target in glioblastoma treatment.
SN - 2073-4409
ER -