An unexpected role of CLASP1 in radiation response and S-phase regulation of head and neck cancer cells

Radiotherapy is a mainstay of treatment for head and neck squamous cell carcinoma (HNSCC), either definitive or adjuvant to surgery. Biological factors known to affect radiation response are hypoxia and DNA repair capacity, but several lines of evidence indicate that other genes and pathways in the...

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Bibliographic Details
Published in:PloS one Vol. 20; no. 8; p. e0329731
Main Authors: de Roest, Reinout H., Buijze, Marijke, Veth, Myrthe, de Lint, Klaas, Pai, Govind, Rooimans, Martin A., Wolthuis, Rob M.F., Brink, Arjen, Poell, Jos B., Brakenhoff, Ruud H.
Format: Journal Article
Language:English
Published: United States Public Library of Science 06.08.2025
Public Library of Science (PLoS)
Subjects:
Biology and life sciences
Cancer
Cancer therapies
Cell cycle
Cell death
Cell Line, Tumor
Chromosomes
CRISPR
CRISPR-Cas Systems
Damage detection
Deoxyribonucleic acid
DNA
DNA damage
DNA Damage - radiation effects
DNA repair
Functional analysis
Gene Expression Regulation, Neoplastic - radiation effects
Gene Knockout Techniques
Genes
Genomes
Head & neck cancer
Head and neck carcinoma
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - pathology
Head and Neck Neoplasms - radiotherapy
Human papillomavirus
Humans
Hypoxia
Medicine and Health Sciences
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Mutation
Physical Sciences
Radiation damage
Radiation therapy
Radiation Tolerance - genetics
Research and Analysis Methods
S Phase - genetics
S Phase - radiation effects
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck - genetics
Toxicity
Tumor cells
Tumors
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Radiotherapy is a mainstay of treatment for head and neck squamous cell carcinoma (HNSCC), either definitive or adjuvant to surgery. Biological factors known to affect radiation response are hypoxia and DNA repair capacity, but several lines of evidence indicate that other genes and pathways in the tumor cells might be involved that have not been elucidated. Here, we report the results of a genome-wide CRISPR-Cas9 functional genomics screen in HNSCC cells to identify radiosensitizing genes. Remarkably, microtubule organizing genes were identified with CLASP1 as most unexpected radiosensitizing hit. Clonogenic assay confirmed the radiosensitizing effect of CLASP1 knockout. Functional analysis showed that CLASP1 knockout has major impact during S-phase, and resulted in mitotic cells with broken chromosomes and cell death. CLASP1 and possibly the microtubule machinery in broader sense seem involved in protection of HNSCC cells against radiation–induced DNA damage. This newly identified mechanism provides an outlook for novel treatment approaches in HNSCC.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0329731