Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma

2014 ◽  
Vol 40 (5) ◽  
pp. 564-569 ◽  
Author(s):  
H. J. Cha ◽  
D. B. Lee ◽  
H. N. Jung ◽  
Y. S. Choi ◽  
H. S. Suh
Keyword(s):  
Dna Damage ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Dna Damage Response ◽  
Squamous Cell ◽  
Actinic Keratosis ◽  
Damage Response ◽  
Werner Protein ◽  
Bowen Disease

scholarly journals The DNA Damage Response Is Differentially Involved in HPV-Positive and HPV-Negative Radioresistant Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3717
Author(s):  
Marieke Bamps ◽  
Rüveyda Dok ◽  
Sandra Nuyts
Keyword(s):  
Dna Damage ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Dna Damage Response ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Damage Response

Radioresistance is a major cause of recurrences and radiotherapy (RT) failure in head and neck squamous cell carcinoma (HNSCC). DNA damage response (DDR) is known to be important for RT response, but its role in radioresistance is not fully understood. Here, we assessed the role of DDR in the radioresistance process of HNSCC by generating radioresistant clones from both HPV-positive SCC154 and HPV-negative SCC61 cells. We show that fractionated RT decreased RT response of HPV-positive and HPV-negative radioresistant clones in vitro and in vivo. Moreover, HPV-positive and HPV-negative radioresistant clones were characterized by differential DDR response. HPV-positive radioresistant clones showed less residual double-strand break damage and increased G2/M arrest recovery after RT, indicating an acquisition of increased DDR kinetics. In contrast, HPV-negative radioresistant clones showed less micronucleated cells after RT and increased survival upon checkpoint inhibition, indicating an increased replicative capacity. Inhibiting key factors of DDR in combination with RT rescued the radioresistant phenotype of both HPV-positive and HPV-negative radioresistant clones. Altogether, our results not only highlight the importance of DDR response in the radioresistance process of HPV-positive and HPV-negative HNSCC, but also provide possibilities for new therapies for HNSCC patients in recurrent settings.

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