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Updated: Jun 20, 2026

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Published on: February 9, 2024
Hyperphosphorylation of replication protein A in cisplatin-resistant and -sensitive head and neck squamous cell
Karoline C Manthey1, Jason G Glanzer, Diana D Dimitrova
1Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska, USA.
Background:
Resistance to chemotherapy is a major limitation in the treatment of head and neck squamous cell carcinomas (HNSCCs), accounting for high mortality rates in patients. Here, we investigated the role of replication protein A (RPA) in cisplatin and etoposide resistance.
Methods:
We used 6 parental HNSCC cell lines. We also generated 1 cisplatin-resistant progeny subline from a parental cisplatin-sensitive cell line, to examine cisplatin resistance and sensitivity with respect to RPA2 hyperphosphorylation and cell-cycle response.
Results:
Cisplatin-resistant HNSCC cell levels of hyperphosphorylated RPA2 in response to cisplatin were 80% to 90% greater compared with cisplatin-sensitive cell lines. RPA2 hyperphosphorylation could be induced in the cisplatin-resistant HNSCC subline. The absence of RPA2 hyperphosphorylation correlated with a defect in cell-cycle progression and cell survival.
Conclusion:
Loss of RPA2 hyperphosphorylation occurs in HNSCC cells and may be a marker of cellular sensitivities to cisplatin and etoposide in HNSCC.
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