SET protein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy
| Autor: | André L. Queiroz, Andréia Machado Leopoldino, Marinaldo Pacífico Cavalcanti-Neto, Valéria Tudella Uyemura, Carlos Curti, Amanda Tomie Ouchida, Sérgio Akira Uyemura, Verônica Soares Brauer, Lucas Oliveira Sousa |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death Cell Survival Apoptosis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Autophagy DNA-(Apurinic or Apyrimidinic Site) Lyase medicine Humans Histone Chaperones Molecular Biology Cellular localization ESTRESSE OXIDATIVO Squamous Cell Carcinoma of Head and Neck Chemistry Cell Biology Protein phosphatase 2 medicine.disease Head and neck squamous-cell carcinoma DNA-Binding Proteins Oxidative Stress stomatognathic diseases 030104 developmental biology Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer research Oxidation-Reduction Intracellular Transcription Factors |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0167-4889 |
| Popis: | Molecular alterations in cell death pathways and imbalances in regulators of up- or downstream signaling pathways can lead to resistance to cell death, which is one of the hallmarks of cancer. These signaling modifications are strategies that tumor cells use to resist chemotherapy and that contribute to the high recurrence rate of head and neck squamous cell carcinoma (HNSCC). The SET oncoprotein is a PP2A inhibitor that accumulates in HNSCC and represents a promising therapeutic target. Here we report the role that SET protein plays in resistance to death of two HNSCC cell lines: Cal 27 and HN13. SET protein regulated intracellular redox balance by controlling cellular localization of APE 1 - an endonuclease that is part of the SET complex and regulates antioxidant gene transcription. SET protein knockdown (siSET) associated with tert-butyl hydroperoxide-induced oxidative stress sensitized Cal 27 and HN13 cells to apoptosis via the extrinsic and intrinsic pathways, respectively. SET protein upregulated autophagy in HNSCC cells in a PP2A-dependent manner and apparently regulated ULK1 expression. The fact that siSET lowered Bcl-2 phosphorylation levels indicated that SET protein interfered with an alternative pathway that modulated autophagy in HNSCC cells. Overall, SET protein regulated intracellular redox state and sustained autophagy in HNSCC cells, which may explain resistance to death of HNSCC cells. Altogether, the findings reported herein support SET protein as therapeutic target for HNSCC. |
| Databáze: | OpenAIRE |
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