Adaptive metabolic rewiring to chronic SFK inhibition

Autores
Pinedo Carpio, Edgar; Davidson, David; Martinez Marignac, Veronica Lucrecia; Panasci, Justin; Aloyz, Raquel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Src family kinases (SFK) are key regulators of cellular proliferation, differentiation, survival, motility and angiogenesis. As such, SFK inhibitors are being tested in clinical trials to prevent metastasis as an alternative to current treatment regimens for a variety of cancers including breast cancer. To contribute to the development of molecular tools improving SFK-targeted therapies, we used the SFK inhibitor dasatinib and a well characterized triple negative breast cancer cell line (BT20). Comparison of the response of BT20 cells with acquired resistance to dasatinib and its? parental counterpart suggest that chronic exposure to SFK inhibition results in increased dependency on TGFβ signaling for proliferation, both in the absence or the presence of dasatinib. In addition, we found that acquired (but not de novo) resistance to dasatinib was reduced by non-cytotoxic concentrations compounds hindering on PI3K, mTORC1 signaling, endoplasmic reticulum stress or autophagy.
Fil: Pinedo Carpio, Edgar. McGill University; Canadá. Jewish General Hospital; Canadá
Fil: Davidson, David. McGill University; Canadá. Jewish General Hospital; Canadá
Fil: Martinez Marignac, Veronica Lucrecia. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentina
Fil: Panasci, Justin. Jewish General Hospital; Canadá. McGill University; Canadá
Fil: Aloyz, Raquel. Jewish General Hospital; Canadá. McGill University; Canadá
Materia
METABOLISM
CANCER
ADQUIRED RESISTANCE
PI3K
SKF INHIBITOR
TGFB
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:11336/65101
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/65101
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Adaptive metabolic rewiring to chronic SFK inhibitionPinedo Carpio, EdgarDavidson, DavidMartinez Marignac, Veronica LucreciaPanasci, JustinAloyz, RaquelMETABOLISMCANCERADQUIRED RESISTANCEPI3KSKF INHIBITORTGFBhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Src family kinases (SFK) are key regulators of cellular proliferation, differentiation, survival, motility and angiogenesis. As such, SFK inhibitors are being tested in clinical trials to prevent metastasis as an alternative to current treatment regimens for a variety of cancers including breast cancer. To contribute to the development of molecular tools improving SFK-targeted therapies, we used the SFK inhibitor dasatinib and a well characterized triple negative breast cancer cell line (BT20). Comparison of the response of BT20 cells with acquired resistance to dasatinib and its? parental counterpart suggest that chronic exposure to SFK inhibition results in increased dependency on TGFβ signaling for proliferation, both in the absence or the presence of dasatinib. In addition, we found that acquired (but not de novo) resistance to dasatinib was reduced by non-cytotoxic concentrations compounds hindering on PI3K, mTORC1 signaling, endoplasmic reticulum stress or autophagy.Fil: Pinedo Carpio, Edgar. McGill University; Canadá. Jewish General Hospital; CanadáFil: Davidson, David. McGill University; Canadá. Jewish General Hospital; CanadáFil: Martinez Marignac, Veronica Lucrecia. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Panasci, Justin. Jewish General Hospital; Canadá. McGill University; CanadáFil: Aloyz, Raquel. Jewish General Hospital; Canadá. McGill University; CanadáImpact Journals2017-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/65101Pinedo Carpio, Edgar; Davidson, David; Martinez Marignac, Veronica Lucrecia; Panasci, Justin; Aloyz, Raquel; Adaptive metabolic rewiring to chronic SFK inhibition; Impact Journals; OncoTarget; 8; 40; 9-2017; 66758-667681949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.8146info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=8146&path[]=24004info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T09:41:48Zoai:ri.conicet.gov.ar:11336/65101instacron: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:34982025-11-05 09:41:48.998CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Adaptive metabolic rewiring to chronic SFK inhibition
title Adaptive metabolic rewiring to chronic SFK inhibition
spellingShingle Adaptive metabolic rewiring to chronic SFK inhibition
Pinedo Carpio, Edgar
METABOLISM
CANCER
ADQUIRED RESISTANCE
PI3K
SKF INHIBITOR
TGFB
title_short Adaptive metabolic rewiring to chronic SFK inhibition
title_full Adaptive metabolic rewiring to chronic SFK inhibition
title_fullStr Adaptive metabolic rewiring to chronic SFK inhibition
title_full_unstemmed Adaptive metabolic rewiring to chronic SFK inhibition
title_sort Adaptive metabolic rewiring to chronic SFK inhibition
dc.creator.none.fl_str_mv Pinedo Carpio, Edgar
Davidson, David
Martinez Marignac, Veronica Lucrecia
Panasci, Justin
Aloyz, Raquel
author Pinedo Carpio, Edgar
author_facet Pinedo Carpio, Edgar
Davidson, David
Martinez Marignac, Veronica Lucrecia
Panasci, Justin
Aloyz, Raquel
author_role author
author2 Davidson, David
Martinez Marignac, Veronica Lucrecia
Panasci, Justin
Aloyz, Raquel
author2_role author
author
author
author
dc.subject.none.fl_str_mv METABOLISM
CANCER
ADQUIRED RESISTANCE
PI3K
SKF INHIBITOR
TGFB
topic METABOLISM
CANCER
ADQUIRED RESISTANCE
PI3K
SKF INHIBITOR
TGFB
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Src family kinases (SFK) are key regulators of cellular proliferation, differentiation, survival, motility and angiogenesis. As such, SFK inhibitors are being tested in clinical trials to prevent metastasis as an alternative to current treatment regimens for a variety of cancers including breast cancer. To contribute to the development of molecular tools improving SFK-targeted therapies, we used the SFK inhibitor dasatinib and a well characterized triple negative breast cancer cell line (BT20). Comparison of the response of BT20 cells with acquired resistance to dasatinib and its? parental counterpart suggest that chronic exposure to SFK inhibition results in increased dependency on TGFβ signaling for proliferation, both in the absence or the presence of dasatinib. In addition, we found that acquired (but not de novo) resistance to dasatinib was reduced by non-cytotoxic concentrations compounds hindering on PI3K, mTORC1 signaling, endoplasmic reticulum stress or autophagy.
Fil: Pinedo Carpio, Edgar. McGill University; Canadá. Jewish General Hospital; Canadá
Fil: Davidson, David. McGill University; Canadá. Jewish General Hospital; Canadá
Fil: Martinez Marignac, Veronica Lucrecia. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentina
Fil: Panasci, Justin. Jewish General Hospital; Canadá. McGill University; Canadá
Fil: Aloyz, Raquel. Jewish General Hospital; Canadá. McGill University; Canadá
description Src family kinases (SFK) are key regulators of cellular proliferation, differentiation, survival, motility and angiogenesis. As such, SFK inhibitors are being tested in clinical trials to prevent metastasis as an alternative to current treatment regimens for a variety of cancers including breast cancer. To contribute to the development of molecular tools improving SFK-targeted therapies, we used the SFK inhibitor dasatinib and a well characterized triple negative breast cancer cell line (BT20). Comparison of the response of BT20 cells with acquired resistance to dasatinib and its? parental counterpart suggest that chronic exposure to SFK inhibition results in increased dependency on TGFβ signaling for proliferation, both in the absence or the presence of dasatinib. In addition, we found that acquired (but not de novo) resistance to dasatinib was reduced by non-cytotoxic concentrations compounds hindering on PI3K, mTORC1 signaling, endoplasmic reticulum stress or autophagy.
publishDate 2017
dc.date.none.fl_str_mv 2017-09
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/11336/65101
Pinedo Carpio, Edgar; Davidson, David; Martinez Marignac, Veronica Lucrecia; Panasci, Justin; Aloyz, Raquel; Adaptive metabolic rewiring to chronic SFK inhibition; Impact Journals; OncoTarget; 8; 40; 9-2017; 66758-66768
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/65101
identifier_str_mv Pinedo Carpio, Edgar; Davidson, David; Martinez Marignac, Veronica Lucrecia; Panasci, Justin; Aloyz, Raquel; Adaptive metabolic rewiring to chronic SFK inhibition; Impact Journals; OncoTarget; 8; 40; 9-2017; 66758-66768
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.8146
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=8146&path[]=24004
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 Impact Journals
publisher.none.fl_str_mv Impact Journals
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 13.087074

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