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An unexpected role of CLASP1 in radiation response and S-phase regulation of head and neck cancer cells
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An unexpected role of CLASP1 in radiation response and S-phase regulation of head and neck cancer cells
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Journal Article
An unexpected role of CLASP1 in radiation response and S-phase regulation of head and neck cancer cells
2025
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Cancer
/ CRISPR
/ DNA
/ DNA Damage - radiation effects
/ Gene Expression Regulation, Neoplastic - radiation effects
/ Genes
/ Genomes
/ Head and Neck Neoplasms - genetics
/ Head and Neck Neoplasms - metabolism
/ Head and Neck Neoplasms - pathology
/ Head and Neck Neoplasms - radiotherapy
/ Humans
/ Hypoxia
/ Medicine and Health Sciences
/ Microtubule-Associated Proteins - genetics
/ Microtubule-Associated Proteins - metabolism
/ Mutation
/ Radiation Tolerance - genetics
/ Research and Analysis Methods
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Toxicity
/ Tumors
