Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development

Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development

Author Monteiro, Hugo P. Autor UNIFESP Google Scholar
Ogata, Fernando T. Autor UNIFESP Google Scholar
Stern, Arnold Google Scholar
Abstract Accumulating mutations may drive cells into the acquisition of abnormal phenotypes that are characteristic of cancer cells. Cancer cells feature profound alterations in proliferation programs that result in a new population of cells that overrides normal tissue construction and maintenance programs. To achieve this goal, cancer cells are endowed with up regulated survival signaling pathways. They also must counteract the cytotoxic effects of high levels of nitric oxide (NO) and of reactive oxygen species (ROS), which are by products of cancer cell growth. Accumulating experimental evidence associates cancer cell survival with their capacity to up-regulate antioxidant systems. Elevated expression of the antioxidant protein thioredoxin-1 (Trx1) has been correlated with cancer development. Trx1 has been characterized as a multifunctional protein, playing different roles in different cell compartments. Trx1 migrates to the nucleus in cells exposed to nitrosative/oxidative stress conditions. Trx1 nuclear migration has been related to the activation of transcription factors associated with cell survival and cell proliferation. There is a direct association between the p21Ras-ERK1/2 MAP Kinases survival signaling pathway and Trx1 nuclear migration under nitrosative stress. The expression of the cytoplasmic protein, the thioredoxin-interacting protein (Txnip), determines the change in Trx1 cellular compartmentalization. The anti-apoptotic actions of Trx1 and its denitrosylase activity occur in the cytoplasm and serve as important regulators of cell survival. Within this context, this review focuses on the participation of Trx1 in cells under nitrosative/oxidative stress in survival signaling pathways associated with cancer development.
Keywords Thioredoxin-1
Nitric oxide
Survival signaling
Cancer development
Language English
Sponsor Brazilian Funding Institutions: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2007/59617-6
FAPESP: 2009/52730-7
FAPESP: 2012/10470-1
CNPq: 481154/2013-2
Date 2017
Published in Biomedical Journal. Amsterdam, v. 40, n. 4, p. 189-199, 2017.
ISSN 2319-4170 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 189-199
Access rights Open access Open Access
Type Revisão
Web of Science ID WOS:000411565000002

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