Autophagy inhibition as a promising therapeutic target for laryngeal cancer

被引:24
作者
Garcia-Mayea, Yoelsis [1 ]
Mir, Cristina [1 ]
Munoz, Lisandra [1 ]
Benavente, Sergi [1 ]
Castellvi, Josep [1 ]
Temprana, Jordi [1 ]
Maggio, Valentina [2 ]
Lorente, Juan [3 ]
Paciucci, Rosanna [2 ]
LLeonart, Matilde E. [1 ,4 ]
机构
[1] Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Biomed Res Canc Stem Cells Grp, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
[2] Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Biomed Res Grp Urol, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
[3] Hosp Vall dHebron HUVH, Otorhinolaryngol Dept, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
[4] CIBERONC, Spanish Biomed Res Network Ctr Oncol, Madrid, Spain
关键词
EXPRESSION; RESISTANCE; HEAD; ACCUMULATION; CHEMOTHERAPY; RISK; P62;
D O I
10.1093/carcin/bgz080
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To identify the putative relevance of autophagy in laryngeal cancer, we performed an immunohistochemistry study to analyze the expression of the proteins involved in this process, namely, LC3, ATG5 and p62/SQSTM1. Additionally, Prostate tumor-overexpressed gene 1 protein (PTOV1) was included due to its potential relevance in laryngeal cancer. Moreover, as cancer resistance might involve autophagy in some circumstances, we studied the intrinsic drug resistance capacity of primary tumor cultures derived from 13 laryngeal cancer biopsies and their expression levels of LC3, ATG5, p62 and PTOV1. Overall, our results suggest that (i) cytoplasmic p62 and PTOV1 can be considered prognostic markers in laryngeal cancer, (ii) the acquisition of resistance seems to be related to PTOV1 and autophagy-related protein overexpression, (iii) by increasing autophagy, PTOV1 might contribute to resistance in this model and (iv) the expression of autophagy-related proteins could classify a subgroup of laryngeal cancer patients who will benefit from a therapy based upon autophagy inhibition. Our study suggests that autophagy inhibition with hydroxychloroquine could be a promising strategy for laryngeal cancer patients, particularly those patients with high resistance to the CDDP treatment that in addition have autophagy upregulation.
引用
收藏
页码:1525 / 1534
页数:10
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