dc.contributor
Institut Català de la Salut
dc.contributor
[Rajagopal MU, Bansal S] Department of Oncology, Georgetown University Medical Center, Washington, USA. [Kaur P] Department of Botany, Khalsa College, Amritsar, India. [Jain SK] Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, India. [Altadil T] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Hinzman CP] Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, USA
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Rajagopal, Meena
dc.contributor.author
Bansal, Shivani
dc.contributor.author
Kaur, Prabhjit
dc.contributor.author
Jain, Shreyans K.
dc.contributor.author
Altadill Vallespi, Tatiana
dc.contributor.author
Hinzman, Charles
dc.date.accessioned
2025-10-24T08:56:57Z
dc.date.available
2025-10-24T08:56:57Z
dc.date.issued
2022-06-20T08:17:48Z
dc.date.issued
2022-06-20T08:17:48Z
dc.date.issued
2021-12-09
dc.identifier
Rajagopal MU, Bansal S, Kaur P, Jain SK, Altadil T, Hinzman CP, et al. TGFβ Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFβ Induced EMT in PDAC. Cancers. 2021 Dec 9;13(24):6204.
dc.identifier
https://hdl.handle.net/11351/7716
dc.identifier
10.3390/cancers13246204
dc.identifier
000736153600001
dc.identifier.uri
http://hdl.handle.net/11351/7716
dc.description.abstract
TGF beta; Pancreatic cancer; Tumor microenvironment
dc.description.abstract
TGF beta; Cancer de pancreas; Microambiente tumoral
dc.description.abstract
TGF beta; Càncer de pàncrees; Microambient tumoral
dc.description.abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy wherein a majority of patients present metastatic disease at diagnosis. Although the role of epithelial to mesenchymal transition (EMT), mediated by transforming growth factor beta (TGFβ), in imparting an aggressive phenotype to PDAC is well documented, the underlying biochemical pathway perturbations driving this behaviour have not been elucidated. We used high-resolution mass spectrometry (HRMS) based molecular phenotyping approach in order to delineate metabolic changes concomitant to TGFβ-induced EMT in pancreatic cancer cells. Strikingly, we observed robust changes in amino acid and energy metabolism that may contribute to tumor invasion and metastasis. Somewhat unexpectedly, TGFβ treatment resulted in an increase in intracellular levels of retinoic acid (RA) that in turn resulted in increased levels of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (COL1). These findings were further validated in plasma samples obtained from patients with resectable pancreatic cancer. Taken together, these observations provide novel insights into small molecule dysregulation that triggers a molecular cascade resulting in increased EMT-like changes in pancreatic cancer cells, a paradigm that can be potentially targeted for better clinical outcomes.
dc.description.abstract
This study was supported by American Cancer Society (IRG-92-152-17 award number AWD4470404), Georgetown Lombardi Comprehensive Cancer Center Support Grant Developmental Funds and Ruesch Foundation to K.U. and A.K.C.
dc.format
application/pdf
dc.format
application/pdf
dc.relation
Cancers;13(24)
dc.relation
https://doi.org/10.3390/cancers13246204
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Pàncrees - Càncer
dc.subject
Metabolisme - Trastorns
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Factors de creixement - Metabolisme
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Transforming Growth Factor beta
dc.subject
Other subheadings::Other subheadings::Other subheadings::/metabolism
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms
dc.subject
PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Transdifferentiation::Epithelial-Mesenchymal Transition
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos y proteínas de señalización intercelular::citocinas::factor de crecimiento transformador beta
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo
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ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas
dc.subject
FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::transdiferenciación celular::transición epiteliomesenquimatosa
dc.title
TGFβ Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFβ Induced EMT in PDAC
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
