Cell Lineage Infidelity in PDAC Progression and Therapy Resistance

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...

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Autores principales:	Antonia Malinova, Lisa Veghini, Francisco X. Real, Vincenzo Corbo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PDAC pancreatic ductal adenocarcinoma organoid culture cell lineage progression therapy resistance Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fcd242144c6d44caa733c5e01c4b254d
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spelling	oai:doaj.org-article:fcd242144c6d44caa733c5e01c4b254d2021-12-02T10:58:37ZCell Lineage Infidelity in PDAC Progression and Therapy Resistance2296-634X10.3389/fcell.2021.795251https://doaj.org/article/fcd242144c6d44caa733c5e01c4b254d2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.795251/fullhttps://doaj.org/toc/2296-634XInfidelity 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.Antonia MalinovaLisa VeghiniFrancisco X. RealFrancisco X. RealFrancisco X. RealVincenzo CorboVincenzo CorboFrontiers Media S.A.articlePDACpancreatic ductal adenocarcinomaorganoid culturecell lineageprogressiontherapy resistanceBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PDAC pancreatic ductal adenocarcinoma organoid culture cell lineage progression therapy resistance Biology (General) QH301-705.5
spellingShingle	PDAC pancreatic ductal adenocarcinoma organoid culture cell lineage progression therapy resistance Biology (General) QH301-705.5 Antonia Malinova Lisa Veghini Francisco X. Real Francisco X. Real Francisco X. Real Vincenzo Corbo Vincenzo Corbo Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
description	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.
format	article
author	Antonia Malinova Lisa Veghini Francisco X. Real Francisco X. Real Francisco X. Real Vincenzo Corbo Vincenzo Corbo
author_facet	Antonia Malinova Lisa Veghini Francisco X. Real Francisco X. Real Francisco X. Real Vincenzo Corbo Vincenzo Corbo
author_sort	Antonia Malinova
title	Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
title_short	Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
title_full	Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
title_fullStr	Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
title_full_unstemmed	Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
title_sort	cell lineage infidelity in pdac progression and therapy resistance
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fcd242144c6d44caa733c5e01c4b254d
work_keys_str_mv	AT antoniamalinova celllineageinfidelityinpdacprogressionandtherapyresistance AT lisaveghini celllineageinfidelityinpdacprogressionandtherapyresistance AT franciscoxreal celllineageinfidelityinpdacprogressionandtherapyresistance AT franciscoxreal celllineageinfidelityinpdacprogressionandtherapyresistance AT franciscoxreal celllineageinfidelityinpdacprogressionandtherapyresistance AT vincenzocorbo celllineageinfidelityinpdacprogressionandtherapyresistance AT vincenzocorbo celllineageinfidelityinpdacprogressionandtherapyresistance
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Cell Lineage Infidelity in PDAC Progression and Therapy Resistance

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