Publication
Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5 alpha-dihydrotestosterone regulation
dc.contributor.author | Cardoso, Henrique J. | |
dc.contributor.author | Figueira, Marilia, I | |
dc.contributor.author | Vaz, Catia V. | |
dc.contributor.author | Carvalho, Tiago M. A. | |
dc.contributor.author | Bras, Luis A. | |
dc.contributor.author | Madureira, Patricia | |
dc.contributor.author | Oliveira, Paulo J. | |
dc.contributor.author | Sardao, Vilma A. | |
dc.contributor.author | Socorro, Silvia | |
dc.date.accessioned | 2021-09-08T10:58:10Z | |
dc.date.available | 2021-09-08T10:58:10Z | |
dc.date.issued | 2021-04 | |
dc.description.abstract | Purpose Resistance to androgen-deprivation therapies and progression to so-called castrate-resistant prostate cancer (CRPC) remain challenges in prostate cancer (PCa) management and treatment. Among other alterations, CRPC has been associated with metabolic reprogramming driven by androgens. Here, we investigated the role of androgens in regulating glutaminolysis in PCa cells and determined the relevance of this metabolic route in controlling the survival and growth of androgen-sensitive (LNCaP) and CRPC (DU145 and PC3) cells. Methods PCa cells (LNCaP, DU145 and PC3) and 3-month old rats were treated with 5 alpha-dihydrotestosterone (DHT). Alternatively, LNCaP cells were exposed to the glutaminase inhibitor BPTES, alone or in combination with the anti-androgen bicalutamide. Biochemical, Western blot and extracellular flux assays were used to evaluate the viability, proliferation, migration and metabolism of PCa cells in response to DHT treatment or glutaminase inhibition. Results We found that DHT up-regulated the expression of the glutamine transporter ASCT2 and glutaminase, both in vitro in LNCaP cells and in vivo in rat prostate cells. BPTES diminished the viability and migration of PCa cells, while increasing caspase-3 activity. CRPC cells were found to be more dependent on glutamine and more sensitive to glutaminase inhibition. BPTES and bicalutamide co-treatment had an additive effect on suppressing LNCaP cell viability. Finally, we found that inhibition of glutaminolysis differentially affected glycolysis and lipid metabolism in both androgen-sensitive and CRPC cells. Conclusion Our data reveal glutaminolysis as a central metabolic route controlling PCa cell fate and highlight the relevance of targeting glutaminase for CRPC treatment. | |
dc.description.sponsorship | FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I -Strengthening research, technological development and innovation [007491, 029114]; National Funds by the FCT-Foundation for Science and Technology [UID/Multi/00709/2013]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/111351/2015, SFRH/BD/104671/2014, IF/00614/2014/CP12340006]; FCT Investigator contract from the Foundation for Science and Technology (FCT), Portugal [IF/00614/2014]; FCT Research Center grant | |
dc.description.version | info:eu-repo/semantics/publishedVersion | |
dc.identifier.doi | 10.1007/s13402-020-00575-9 | |
dc.identifier.issn | 2211-3428 | |
dc.identifier.uri | http://hdl.handle.net/10400.1/17048 | |
dc.language.iso | eng | |
dc.peerreviewed | yes | |
dc.publisher | SPRINGER | |
dc.relation | International comparisons of product supply chains in the agro-food sectors: determinants of their competitiveness and performance on EU and international markets | |
dc.relation | Health Sciences Research Centre | |
dc.relation | Androgens/anti-androgens and glycaemia in reprogramming metabolism of prostate cancer: targeting both androgen receptor and metabolism as a therapeutic option | |
dc.relation | Estrogens and prostate cancer: role of GPER and regulation of stem cell factor SCF/c-KIT system | |
dc.relation | Identification and characterization of redox regulatory proteins involved in cancer progression | |
dc.subject | Prostate cancer | |
dc.subject | Castrate resistance | |
dc.subject | 5 alpha-dihydrotestosterone | |
dc.subject | Bicalutamide | |
dc.subject | BPTES | |
dc.subject | ASCT2 | |
dc.subject | Glutamine | |
dc.subject | Glutaminolysis | |
dc.subject.other | Oncology; Cell Biology; Pathology | |
dc.title | Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5 alpha-dihydrotestosterone regulation | |
dc.type | journal article | |
dspace.entity.type | Publication | |
oaire.awardTitle | International comparisons of product supply chains in the agro-food sectors: determinants of their competitiveness and performance on EU and international markets | |
oaire.awardTitle | Health Sciences Research Centre | |
oaire.awardTitle | Androgens/anti-androgens and glycaemia in reprogramming metabolism of prostate cancer: targeting both androgen receptor and metabolism as a therapeutic option | |
oaire.awardTitle | Estrogens and prostate cancer: role of GPER and regulation of stem cell factor SCF/c-KIT system | |
oaire.awardTitle | Identification and characterization of redox regulatory proteins involved in cancer progression | |
oaire.awardURI | info:eu-repo/grantAgreement/EC/FP7/312029/EU | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F00709%2F2013/PT | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH%2FBD%2F111351%2F2015/PT | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F104671%2F2014/PT | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00614%2F2014%2FCP1234%2FCT0006/PT | |
oaire.citation.endPage | 403 | |
oaire.citation.issue | 2 | |
oaire.citation.startPage | 385 | |
oaire.citation.title | Cellular Oncology | |
oaire.citation.volume | 44 | |
oaire.fundingStream | FP7 | |
oaire.fundingStream | 6817 - DCRRNI ID | |
oaire.fundingStream | POR_CENTRO | |
oaire.fundingStream | Investigador FCT | |
person.familyName | Madureira | |
person.givenName | Patricia | |
person.identifier.ciencia-id | 6612-9A86-6929 | |
person.identifier.orcid | 0000-0002-4856-3908 | |
person.identifier.scopus-author-id | 10340140500 | |
project.funder.identifier | http://doi.org/10.13039/501100008530 | |
project.funder.identifier | http://doi.org/10.13039/501100001871 | |
project.funder.identifier | http://doi.org/10.13039/501100001871 | |
project.funder.identifier | http://doi.org/10.13039/501100001871 | |
project.funder.identifier | http://doi.org/10.13039/501100001871 | |
project.funder.name | European Commission | |
project.funder.name | Fundação para a Ciência e a Tecnologia | |
project.funder.name | Fundação para a Ciência e a Tecnologia | |
project.funder.name | Fundação para a Ciência e a Tecnologia | |
project.funder.name | Fundação para a Ciência e a Tecnologia | |
rcaap.rights | restrictedAccess | |
rcaap.type | article | |
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