Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10316/101006
Campo DC | Valor | Idioma |
---|---|---|
dc.contributor.author | Sousa, Bárbara | - |
dc.contributor.author | Pereira, Joana | - |
dc.contributor.author | Marques, Ricardo | - |
dc.contributor.author | Grilo, Luís F | - |
dc.contributor.author | Pereira, Susana P | - |
dc.contributor.author | Oliveira, Vilma Marisa Arrojado Soares Sardão | - |
dc.contributor.author | Schmitt, Fernando | - |
dc.contributor.author | Oliveira, Paulo J | - |
dc.contributor.author | Paredes, Joana Cancela de Amorim Falcão | - |
dc.date.accessioned | 2022-07-25T22:59:49Z | - |
dc.date.available | 2022-07-25T22:59:49Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 09254439 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/101006 | - |
dc.description.abstract | Successful metastatic spreading relies on cancer cells with stem-like properties, glycolytic metabolism and increased antioxidant protection, allowing them to escape anoikis and to survive in circulation. The expression of P-cadherin, a poor prognostic factor in breast cancer, is associated with hypoxic, glycolytic and acidosis biomarkers. In agreement, P-cadherin-enriched breast cancer cell populations presents a glycolytic and an acid-resistance phenotype. Our aim was to evaluate whether P-cadherin expression controls the glycolytic and oxidative phosphorylation fluxes of matrix-detached breast cancer cells, acting as an antioxidant and enhancing their survival in anchorage-independent conditions. By using matrix-detached breast cancer cells, we concluded that P-cadherin increases glucose-6-phosphate dehydrogenase expression, up-regulating the carbon flux through the pentose phosphate pathway, while inhibiting pyruvate oxidation to acetyl-coA via pyruvate dehydrogenase kinase-4 (PDK-4) activation. Accordingly, P-cadherin expression conferred increased sensitivity to dichloroacetate (DCA), a PDK inhibitor. P-cadherin expression also regulates oxidative stress in matrix-detached breast cancer cells, through the control of antioxidant systems, such as catalase and superoxide dismutases (SOD)1 and 2, providing these cells with an increased resistance to doxorubicin-induced anoikis. Importantly, this association was validated in primary invasive breast carcinomas, where an enrichment of SOD2 was found in P-cadherin-overexpressing breast carcinomas. In conclusion, we propose that P-cadherin up-regulates carbon flux through the pentose phosphate pathway and decreases oxidative stress in matrix-detached breast cancer cells. These metabolic remodeling and antioxidant roles of P-cadherin can promote the survival of breast cancer cells in circulation and in metastatic sites, being a possible player in breast cancer therapeutic resistance to pro-oxidant-based interventions. | pt |
dc.language.iso | por | pt |
dc.rights | openAccess | pt |
dc.subject | Antioxidant; Breast cancer; Matrix-detached; Oxidative stress; P-cadherin; anoikis-resistant | pt |
dc.subject.mesh | Breast Neoplasms | pt |
dc.subject.mesh | Cadherins | pt |
dc.subject.mesh | Extracellular Matrix | pt |
dc.subject.mesh | Female | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Pentose Phosphate Pathway | pt |
dc.subject.mesh | Reactive Oxygen Species | pt |
dc.subject.mesh | Tumor Cells, Cultured | pt |
dc.subject.mesh | Anoikis | pt |
dc.subject.mesh | Oxidative Stress | pt |
dc.title | P-cadherin induces anoikis-resistance of matrix-detached breast cancer cells by promoting pentose phosphate pathway and decreasing oxidative stress | pt |
dc.type | article | - |
degois.publication.firstPage | 165964 | pt |
degois.publication.issue | 12 | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1016/j.bbadis.2020.165964 | pt |
degois.publication.volume | 1866 | pt |
dc.date.embargo | 2020-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | pt | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-7014-4614 | - |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
Sousa et al. - 2020 - Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease-annotated.pdf | 5.27 MB | Adobe PDF | Ver/Abrir |
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