Downregulation of Snail by DUSP1 Impairs Cell Migration and Invasion through the Inactivation of JNK and ERK and Is Useful as a Predictive Factor in the Prognosis of Prostate Cancer
Authors
Martínez Martínez, Desirée; Baquero Valls, Pablo; Toledo Lobo, María Del Val; Ropero Salinas, Santiago; Angulo Cuesta, Javier; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/58834DOI: 10.3390/cancers13051158
ISSN: 2072-6694
Date
2021-03Affiliation
Universidad de Alcalá. Departamento de Bioquímica y Biología Molecular; Universidad de Alcalá. Departamento de Biología de SistemasFunders
Universidad Autónoma de Madrid
Comunidad de Madrid
Bibliographic citation
Cancers, 2021, v. 13, n. 5, p. 1158-
Keywords
DUSP1
MAPK
Snail
Prostate cancer
Migration and invasion
Patient survival
Biomarkers
Description / Notes
21 p.
Project
info:eu-repo/grantAgreement/UAM/ Post-Master Program of Dpt. Biochemistry //ES//
info:eu-repo/grantAgreement/CAM//PEJD-2018-PRE%2FBMD-8987/ES//
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© 2021 by the authors. Licensee MDPI
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Dual specificity phosphatase 1 (DUSP1) is crucial in prostate cancer (PC), since its ex pression is downregulated in advanced carcinomas. Here, we investigated DUSP1 effects on the expression of mesenchymal marker Snail, cell migration and invasion, analyzing the underlying mechanisms mediated by mitogen-activated protein kinases (MAPKs) inhibition. To this purpose, we used different PC cells overexpressing or lacking DUSP1 or incubated with MAPKs inhibitors. Moreover, we addressed the correlation of DUSP1 expression with Snail and activated MAPKs levels in samples from patients diagnosed with benign hyperplasia or prostate carcinoma, studying its implication in tumor prognosis and survival. We found that DUSP1 downregulates Snail expression and impairs migration and invasion in PC cells. Similar results were obtained following the inhi bition of c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK). In clinical samples, we evidenced an inverse correlation between DUSP1 expression and Snail levels, which are further associated with JNK and ERK activation. Consequently, the pattern DUSP1high/activated JNKlow/activated ERKlow/Snaillow is associated with an overall extended survival of PC patients. In summary, the ratio between DUSP1 and Snail expression, with additional JNK and ERK activity measurement, may serve as a potential biomarker to predict the clinical outcome of PC patients. Furthermore, DUSP1 induction or inhibition of JNK and ERK pathways could be useful to treat PC.
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