Autophagy inhibition as a promising therapeutic target for laryngeal cancer

  1. Garcia-Mayea, Yoelsis 2
  2. Mir, Cristina 2
  3. Muñoz, Lisandra 2
  4. Benavente, Sergi 2
  5. Castellvi, Josep 2
  6. Temprana, Jordi 2
  7. Maggio, Valentina 1
  8. Lorente, Juan 4
  9. Paciucci, Rosanna 1
  10. LLeonart, Matilde E 23
  1. 1 Otorhinolaryngology Department, Hospital Vall d´Hebron (HUVH), Passeig Vall d´Hebron, Barcelona, Spain
  2. 2 Biomedical Research in Cancer Stem Cells Group, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d´Hebron, Barcelona, Spain
  3. 3 Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Madrid, Spain
  4. 4 Biomedical Research Group of Urology, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d´Hebron, Barcelona, Spain
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Revista:
Carcinogenesis

ISSN: 0143-3334,  1460-2180

Año de publicación: 2019

Volumen: 40

Número: 12

Páginas: 1525-1534

Tipo: Artículo

DOI: 10.1093/CARCIN/BGZ080 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Carcinogenesis

Resumen

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.

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