A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.

Autores
Rodriguez, Matias Exequiel; Catrinacio, Cintia Betiana; Ropolo, Alejandro Javier; Rivarola, Viviana Alicia; Vaccaro, Maria Ines
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumor and leads to chemo/radio resistance. Recently, it has been shown that in response to hypoxia cell can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment. Moreover, hypoxia and autophagy have been implicated in resistance to antitumor PDT. However, the molecular signals by which HIF-1α induces autophagy in PDT context has not been studied yet. Here we evaluate theinterplay between HIF-1α and autophagy as well as the underlying mechanism in the PDT resistance of colon cancer cells. Our study demonstrates that HIF-1α stabilization significantly increases VMP1-related autophagy through binding to hypoxia responsive elements in VMP1 promoter. We show that HIF-1α-induced utophagy increases colon cancer cell survival as well as decreses cell death after PDT. Moreover, here we demonstrate that HIF-1α-induced autophagy is mediated by VMP1 expression, since downregulation of VMP1 by RNA interference strategy reduces HIF-1α-induced autophagy and cell survival after PDT. In conclusion, PDT induces autophagy as a survival mechanism and the induction of the novel HIF-1α/VMP1/autophagic pathway may explain, at least in part, theresistance of colon cancer cells to PDT. The knowledge of the molecular mechanisms involved in PDT resistance may lead to more accurate therapeutic strategies.
Fil: Rodriguez, Matias Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad Nacional de Río Cuarto; Argentina
Fil: Catrinacio, Cintia Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Ropolo, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Rivarola, Viviana Alicia. Universidad Nacional de Río Cuarto; Argentina
Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Materia
COLON CANCER
PHOTODYNAMIC THERAPY
HIF-1ALPHA
VMP1
AUTOPHAGY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47432
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47432
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.Rodriguez, Matias ExequielCatrinacio, Cintia BetianaRopolo, Alejandro JavierRivarola, Viviana AliciaVaccaro, Maria InesCOLON CANCERPHOTODYNAMIC THERAPYHIF-1ALPHAVMP1AUTOPHAGYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumor and leads to chemo/radio resistance. Recently, it has been shown that in response to hypoxia cell can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment. Moreover, hypoxia and autophagy have been implicated in resistance to antitumor PDT. However, the molecular signals by which HIF-1α induces autophagy in PDT context has not been studied yet. Here we evaluate theinterplay between HIF-1α and autophagy as well as the underlying mechanism in the PDT resistance of colon cancer cells. Our study demonstrates that HIF-1α stabilization significantly increases VMP1-related autophagy through binding to hypoxia responsive elements in VMP1 promoter. We show that HIF-1α-induced utophagy increases colon cancer cell survival as well as decreses cell death after PDT. Moreover, here we demonstrate that HIF-1α-induced autophagy is mediated by VMP1 expression, since downregulation of VMP1 by RNA interference strategy reduces HIF-1α-induced autophagy and cell survival after PDT. In conclusion, PDT induces autophagy as a survival mechanism and the induction of the novel HIF-1α/VMP1/autophagic pathway may explain, at least in part, theresistance of colon cancer cells to PDT. The knowledge of the molecular mechanisms involved in PDT resistance may lead to more accurate therapeutic strategies.Fil: Rodriguez, Matias Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad Nacional de Río Cuarto; ArgentinaFil: Catrinacio, Cintia Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Ropolo, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Rivarola, Viviana Alicia. Universidad Nacional de Río Cuarto; ArgentinaFil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaRoyal Society of Chemistry2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47432Rodriguez, Matias Exequiel; Catrinacio, Cintia Betiana; Ropolo, Alejandro Javier; Rivarola, Viviana Alicia; Vaccaro, Maria Ines; A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.; Royal Society of Chemistry; Photochemical and Photobiological Sciences; 16; 8-2017; 1631-16421474-905XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1039/C7PP00161Dinfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2017/PP/C7PP00161D#!divAbstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:20:54Zoai:ri.conicet.gov.ar:11336/47432instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:20:55.119CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
title A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
spellingShingle A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
Rodriguez, Matias Exequiel
COLON CANCER
PHOTODYNAMIC THERAPY
HIF-1ALPHA
VMP1
AUTOPHAGY
title_short A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
title_full A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
title_fullStr A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
title_full_unstemmed A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
title_sort A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.
dc.creator.none.fl_str_mv Rodriguez, Matias Exequiel
Catrinacio, Cintia Betiana
Ropolo, Alejandro Javier
Rivarola, Viviana Alicia
Vaccaro, Maria Ines
author Rodriguez, Matias Exequiel
author_facet Rodriguez, Matias Exequiel
Catrinacio, Cintia Betiana
Ropolo, Alejandro Javier
Rivarola, Viviana Alicia
Vaccaro, Maria Ines
author_role author
author2 Catrinacio, Cintia Betiana
Ropolo, Alejandro Javier
Rivarola, Viviana Alicia
Vaccaro, Maria Ines
author2_role author
author
author
author
dc.subject.none.fl_str_mv COLON CANCER
PHOTODYNAMIC THERAPY
HIF-1ALPHA
VMP1
AUTOPHAGY
topic COLON CANCER
PHOTODYNAMIC THERAPY
HIF-1ALPHA
VMP1
AUTOPHAGY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumor and leads to chemo/radio resistance. Recently, it has been shown that in response to hypoxia cell can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment. Moreover, hypoxia and autophagy have been implicated in resistance to antitumor PDT. However, the molecular signals by which HIF-1α induces autophagy in PDT context has not been studied yet. Here we evaluate theinterplay between HIF-1α and autophagy as well as the underlying mechanism in the PDT resistance of colon cancer cells. Our study demonstrates that HIF-1α stabilization significantly increases VMP1-related autophagy through binding to hypoxia responsive elements in VMP1 promoter. We show that HIF-1α-induced utophagy increases colon cancer cell survival as well as decreses cell death after PDT. Moreover, here we demonstrate that HIF-1α-induced autophagy is mediated by VMP1 expression, since downregulation of VMP1 by RNA interference strategy reduces HIF-1α-induced autophagy and cell survival after PDT. In conclusion, PDT induces autophagy as a survival mechanism and the induction of the novel HIF-1α/VMP1/autophagic pathway may explain, at least in part, theresistance of colon cancer cells to PDT. The knowledge of the molecular mechanisms involved in PDT resistance may lead to more accurate therapeutic strategies.
Fil: Rodriguez, Matias Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad Nacional de Río Cuarto; Argentina
Fil: Catrinacio, Cintia Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Ropolo, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Rivarola, Viviana Alicia. Universidad Nacional de Río Cuarto; Argentina
Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
description Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumor and leads to chemo/radio resistance. Recently, it has been shown that in response to hypoxia cell can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment. Moreover, hypoxia and autophagy have been implicated in resistance to antitumor PDT. However, the molecular signals by which HIF-1α induces autophagy in PDT context has not been studied yet. Here we evaluate theinterplay between HIF-1α and autophagy as well as the underlying mechanism in the PDT resistance of colon cancer cells. Our study demonstrates that HIF-1α stabilization significantly increases VMP1-related autophagy through binding to hypoxia responsive elements in VMP1 promoter. We show that HIF-1α-induced utophagy increases colon cancer cell survival as well as decreses cell death after PDT. Moreover, here we demonstrate that HIF-1α-induced autophagy is mediated by VMP1 expression, since downregulation of VMP1 by RNA interference strategy reduces HIF-1α-induced autophagy and cell survival after PDT. In conclusion, PDT induces autophagy as a survival mechanism and the induction of the novel HIF-1α/VMP1/autophagic pathway may explain, at least in part, theresistance of colon cancer cells to PDT. The knowledge of the molecular mechanisms involved in PDT resistance may lead to more accurate therapeutic strategies.
publishDate 2017
dc.date.none.fl_str_mv 2017-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/47432
Rodriguez, Matias Exequiel; Catrinacio, Cintia Betiana; Ropolo, Alejandro Javier; Rivarola, Viviana Alicia; Vaccaro, Maria Ines; A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.; Royal Society of Chemistry; Photochemical and Photobiological Sciences; 16; 8-2017; 1631-1642
1474-905X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47432
identifier_str_mv Rodriguez, Matias Exequiel; Catrinacio, Cintia Betiana; Ropolo, Alejandro Javier; Rivarola, Viviana Alicia; Vaccaro, Maria Ines; A novel HIF-1α/VMP1-Autophagic Pathway Induces Resistance to Photodynamic Therapy in Colon Cancer Cells.; Royal Society of Chemistry; Photochemical and Photobiological Sciences; 16; 8-2017; 1631-1642
1474-905X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/C7PP00161D
info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2017/PP/C7PP00161D#!divAbstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.48226

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