SET protein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy.

Autor: Ouchida AT; Graduate Program in Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Uyemura VT; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Queiroz AL; Graduate Program in Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Brauer VS; Graduate Program in Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Cavalcanti-Neto MP; Graduate Program in Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Sousa LO; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Uyemura SA; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Curti C; Graduate Program in Biochemistry, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Leopoldino AM; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: andreiaml@usp.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2019 Apr; Vol. 1866 (4), pp. 623-637. Date of Electronic Publication: 2019 Jan 16.
DOI: 10.1016/j.bbamcr.2019.01.005
Abstrakt: 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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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