Mostrar el registro sencillo del ítem
dc.contributor.author
Paradise, Brooke D.
dc.contributor.author
Gainullin, Vladimir
dc.contributor.author
Almada, Luciana
dc.contributor.author
Sigafoos, Ashley
dc.contributor.author
Sen, Sandhya
dc.contributor.author
Vera, Renzo Emanuel
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Raja Arul, Glancis L.
dc.contributor.author
Toruner, Murat
dc.contributor.author
Pease, David R.
dc.contributor.author
Gonzalez, Alina Lujan
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Mentucci, Fátima María
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Grasso, Daniel Hector
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Fernandez Zapico, Martin Ernesto
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.date.available
2024-02-22T12:23:17Z
dc.date.issued
2023-07
dc.identifier.citation
Paradise, Brooke D.; Gainullin, Vladimir; Almada, Luciana; Sigafoos, Ashley; Sen, Sandhya; et al.; SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer; Journal of the Serbian Chemical Society; Biochemical Journal; 480; 15; 7-2023; 1199-1216
dc.identifier.issn
0264-6021
dc.identifier.uri
http://hdl.handle.net/11336/227997
dc.description.abstract
Aberrant activation of the Hedgehog (Hh) signaling pathway, through which the GLI family of transcription factors (TF) is stimulated, is commonly observed in cancer cells. One well-established mechanism of this increased activity is through the inactivation of Suppressor of Fused (SUFU), a negative regulator of the Hh pathway. Relief from negative regulation by SUFU facilitates GLI activity and induction of target gene expression. Here, we demonstrate a novel role for SUFU as a promoter of GLI activity in pancreatic ductal adenocarcinoma (PDAC). In non-ciliated PDAC cells unresponsive to Smoothened agonism, SUFU overexpression increases GLI transcriptional activity. Conversely, knockdown (KD) of SUFU reduces the activity of GLI in PDAC cells. Through array PCR analysis of GLI target genes, we identified B-cell lymphoma 2 (BCL2) among the top candidates down-regulated by SUFU KD. We demonstrate that SUFU KD results in reduced PDAC cell viability, and overexpression of BCL2 partially rescues the effect of reduced cell viability by SUFU KD. Further analysis using as a model GLI1, a major TF activator of the GLI family in PDAC cells, shows the interaction of SUFU and GLI1 in the nucleus through previously characterized domains. Chromatin immunoprecipitation (ChIP) assay shows the binding of both SUFU and GLI1 at the promoter of BCL2 in PDAC cells. Finally, we demonstrate that SUFU promotes GLI1 activity without affecting its protein stability. Through our findings, we propose a novel role of SUFU as a positive regulator of GLI1 in PDAC, adding a new mechanism of Hh/GLI signaling pathway regulation in cancer cells.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Journal of the Serbian Chemical Society
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
PANCREATIC CANCER
dc.subject
GLI
dc.subject
SUFU
dc.subject
HEDGEHOG
dc.subject.classification
Bioquímica y Biología Molecular
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Medicina Básica
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-02-20T12:43:58Z
dc.journal.volume
480
dc.journal.number
15
dc.journal.pagination
1199-1216
dc.journal.pais
Reino Unido
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Londres
dc.description.fil
Fil: Paradise, Brooke D.. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Gainullin, Vladimir. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Almada, Luciana. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Sigafoos, Ashley. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Sen, Sandhya. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Vera, Renzo Emanuel. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Raja Arul, Glancis L.. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Toruner, Murat. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Pease, David R.. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.description.fil
Fil: Gonzalez, Alina Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
dc.description.fil
Fil: Mentucci, Fátima María. Universita di Salerno; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Grasso, Daniel Hector. Instituto de Estudios de la Inmunidad Humoral Profesor Ricardo A. Margni (idehu); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
dc.description.fil
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic Graduate School Of Biomedical Sciences; Argentina
dc.journal.title
Biochemical Journal
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20220439/233309/SUFU-promotes-GLI-activity-in-a-Hedgehog
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1042/BCJ20220439
Archivos asociados