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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Vydáno v:	PloS one Ročník 20; číslo 8; s. e0329731
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 06.08.2025 Public Library of Science (PLoS)
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0329731