Elevated expression of iASPP in head and neck squamous cell carcinoma and its clinical significance

2012 ◽  
Vol 29 (5) ◽  
pp. 3381-3388 ◽  
Author(s):  
Zhengzheng Liu ◽  
Xin Zhang ◽  
Donghai Huang ◽  
Yong Liu ◽  
Xiaozhe Zhang ◽  
...  
2020 ◽  
Vol 20 (6) ◽  
pp. 1-1
Author(s):  
Feng Zhong ◽  
Hui-Ping Lu ◽  
Gang Chen ◽  
Yi-Wu Dang ◽  
Xiao-Guohui Zhang ◽  
...  

Head & Neck ◽  
2013 ◽  
Vol 36 (3) ◽  
pp. 334-339 ◽  
Author(s):  
Raphael E. Alford ◽  
David V. Fried ◽  
Benjamin Y. Huang ◽  
Mark Weissler ◽  
Carol Shores ◽  
...  

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Ulrike Schoetz ◽  
Diana Klein ◽  
Julia Hess ◽  
Seyd Shnayien ◽  
Steffen Spoerl ◽  
...  

AbstractResistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains a perpetual clinical challenge. The underlying mechanisms are manifold and demand for comprehensive, cancer entity- and subtype-specific examination. In the present study, resistance against radiotherapy was systematically assessed in a panel of human head-and-neck squamous cell carcinoma (HNSCC) cell lines and xenotransplants derived thereof with the overarching aim to extract master regulators and potential candidates for mechanism-based pharmacological targeting. Clonogenic survival data were integrated with molecular and functional data on DNA damage repair and different cell fate decisions. A positive correlation between radioresistance and early induction of HNSCC cell senescence accompanied by NF-κB-dependent production of distinct senescence-associated cytokines, particularly ligands of the CXCR2 chemokine receptor, was identified. Time-lapse microscopy and medium transfer experiments disclosed the non-cell autonomous, paracrine nature of these mechanisms, and pharmacological interference with senescence-associated cytokine production by the NF-κB inhibitor metformin significantly improved radiotherapeutic performance in vitro and in vivo. With regard to clinical relevance, retrospective analyses of TCGA HNSCC data and an in-house HNSCC cohort revealed that elevated expression of CXCR2 and/or its ligands are associated with impaired treatment outcome. Collectively, our study identifies radiation-induced tumor cell senescence and the NF-κB-dependent production of distinct senescence-associated cytokines as critical drivers of radioresistance in HNSCC whose therapeutic targeting in the context of multi-modality treatment approaches should be further examined and may be of particular interest for the subgroup of patients with elevated expression of the CXCR2/ligand axis.


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