Cell lineage infidelity in PDAC progression and therapy resistance
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- dc.contributor.author Malinova, Antonia
- dc.contributor.author Veghini, Lisa
- dc.contributor.author Real, Francisco X.
- dc.contributor.author Corbo, Vincenzo
- dc.date.accessioned 2022-01-18T06:53:39Z
- dc.date.available 2022-01-18T06:53:39Z
- dc.date.issued 2021
- dc.description.abstract Infidelity to cell fate occurs when differentiated cells lose their original identity and either revert to a more multipotent state or transdifferentiate into a different cell type, either within the same embryonic lineage or in an entirely different one. Whilst in certain circumstances, such as in wound repair, this process is beneficial, it can be hijacked by cancer cells to drive disease initiation and progression. Cell phenotype switching has been shown to also serve as a mechanism of drug resistance in some epithelial cancers. In pancreatic ductal adenocarcinoma (PDAC), the role of lineage infidelity and phenotype switching is still unclear. Two consensus molecular subtypes of PDAC have been proposed that mainly reflect the existence of cell lineages with different degrees of fidelity to pancreatic endodermal precursors. Indeed, the classical subtype of PDAC is characterised by the expression of endodermal lineage specifying transcription factors, while the more aggressive basal-like/squamous subtype is defined by epigenetic downregulation of endodermal genes and alterations in chromatin modifiers. Here, we summarise the current knowledge of mechanisms (genetic and epigenetic) of cell fate switching in PDAC and discuss how pancreatic organoids might help increase our understanding of both cell-intrinsic and cell-extrinsic factors governing lineage infidelity during the distinct phases of PDAC evolution.
- dc.description.sponsorship VC is supported by the Associazione Italiana Ricerca sul Cancro (AIRC; Grant No. 18178). VC and AM are also supported by the Marie Skłodowska-Curie Actions project PRECODE (Grant No: 861196). Work in the laboratory of FXR is supported, in part, by Grant RTI2018-101071-B-I00 from Ministerio de Ciencia, Innovación y Universidades (Madrid, Spain) (co-funded by the ERDF-EU).
- dc.format.mimetype application/pdf
- dc.identifier.citation Malinova A, Veghini L, Real FX, Corbo V. Cell lineage infidelity in PDAC progression and therapy resistance. Front Cell Dev Biol. 2021;9:795251. DOI: 10.3389/fcell.2021.795251
- dc.identifier.doi http://dx.doi.org/10.3389/fcell.2021.795251
- dc.identifier.issn 2296-634X
- dc.identifier.uri http://hdl.handle.net/10230/52249
- dc.language.iso eng
- dc.publisher Frontiers
- dc.relation.ispartof Front Cell Dev Biol. 2021;9:795251
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/861196
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-101071-B-I00
- dc.rights © 2021 Malinova, Veghini, Real and Corbo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword PDAC
- dc.subject.keyword Cell lineage
- dc.subject.keyword Organoid culture
- dc.subject.keyword Pancreatic ductal adenocarcinoma
- dc.subject.keyword Progression
- dc.subject.keyword Therapy resistance
- dc.title Cell lineage infidelity in PDAC progression and therapy resistance
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion