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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Ouchida, Amanda Tomie [1, 2] ; Uyemura, Valeria Tudella [1] ; Queiroz, Andre Lima [2] ; Brauer, Veronica Soares [3, 2] ; Cavalcanti-Neto, Marinaldo Pacifico [1, 2] ; Sousa, Lucas Oliveira [3] ; Uyemura, Sergio Akira [3] ; Curti, Carlos [1, 2] ; Leopoldino, Andreia Machado [3]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Grad Program Biochem, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Analyses Toxicol & Food Sci, Ribeirao Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1866, n. 4, p. 623-637, APR 2019.
Web of Science Citations: 1
Abstract

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. (AU)

FAPESP's process: 16/19103-2 - SET and sphingolipids in head and neck squamous cell carcinoma: signaling, targets and antiumoral therapy
Grantee:Andréia Machado Leopoldino
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer
Grantee:Carlos Curti
Support type: Regular Research Grants
FAPESP's process: 09/52228-0 - Studies on resistance to apoptosis in cancer, head/neck model: signaling via with emphasis on PIP3-Akt/SET, oxidative stress, mitochondria and relationships
Grantee:Carlos Curti
Support type: Research Projects - Thematic Grants