Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer

Pancreatic cancer is a very aggressive disease with 5-year survival rates of less than 10%. The constantly increasing incidence and stagnant patient outcomes despite changes in treatment regimens emphasize the requirement of a better understanding of the disease mechanisms. Challenges in treating pa...

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Autores principales:	Ruthger van Roey, Thomas Brabletz, Marc P. Stemmler, Isabell Armstark
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ADM—acinar to ductal metaplasia PanIN—pancreatic intraepithelial neoplasia PDAC—pancreatic ductal adenocarcinoma transcription factors (TFs) cellular plasticity epigenetics (chromatin remodelling) Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ee2c60151b584f50933fbe927f90219c
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spelling	oai:doaj.org-article:ee2c60151b584f50933fbe927f90219c2021-11-30T13:37:42ZDeregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer2296-634X10.3389/fcell.2021.753456https://doaj.org/article/ee2c60151b584f50933fbe927f90219c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.753456/fullhttps://doaj.org/toc/2296-634XPancreatic cancer is a very aggressive disease with 5-year survival rates of less than 10%. The constantly increasing incidence and stagnant patient outcomes despite changes in treatment regimens emphasize the requirement of a better understanding of the disease mechanisms. Challenges in treating pancreatic cancer include diagnosis at already progressed disease states due to the lack of early detection methods, rapid acquisition of therapy resistance, and high metastatic competence. Pancreatic ductal adenocarcinoma, the most prevalent type of pancreatic cancer, frequently shows dominant-active mutations in KRAS and TP53 as well as inactivation of genes involved in differentiation and cell-cycle regulation (e.g. SMAD4 and CDKN2A). Besides somatic mutations, deregulated transcription factor activities strongly contribute to disease progression. Specifically, transcriptional regulatory networks essential for proper lineage specification and differentiation during pancreas development are reactivated or become deregulated in the context of cancer and exacerbate progression towards an aggressive phenotype. This review summarizes the recent literature on transcription factor networks and epigenetic gene regulation that play a crucial role during tumorigenesis.Ruthger van RoeyThomas BrabletzMarc P. StemmlerIsabell ArmstarkFrontiers Media S.A.articleADM—acinar to ductal metaplasiaPanIN—pancreatic intraepithelial neoplasiaPDAC—pancreatic ductal adenocarcinomatranscription factors (TFs)cellular plasticityepigenetics (chromatin remodelling)Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ADM—acinar to ductal metaplasia PanIN—pancreatic intraepithelial neoplasia PDAC—pancreatic ductal adenocarcinoma transcription factors (TFs) cellular plasticity epigenetics (chromatin remodelling) Biology (General) QH301-705.5
spellingShingle	ADM—acinar to ductal metaplasia PanIN—pancreatic intraepithelial neoplasia PDAC—pancreatic ductal adenocarcinoma transcription factors (TFs) cellular plasticity epigenetics (chromatin remodelling) Biology (General) QH301-705.5 Ruthger van Roey Thomas Brabletz Marc P. Stemmler Isabell Armstark Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
description	Pancreatic cancer is a very aggressive disease with 5-year survival rates of less than 10%. The constantly increasing incidence and stagnant patient outcomes despite changes in treatment regimens emphasize the requirement of a better understanding of the disease mechanisms. Challenges in treating pancreatic cancer include diagnosis at already progressed disease states due to the lack of early detection methods, rapid acquisition of therapy resistance, and high metastatic competence. Pancreatic ductal adenocarcinoma, the most prevalent type of pancreatic cancer, frequently shows dominant-active mutations in KRAS and TP53 as well as inactivation of genes involved in differentiation and cell-cycle regulation (e.g. SMAD4 and CDKN2A). Besides somatic mutations, deregulated transcription factor activities strongly contribute to disease progression. Specifically, transcriptional regulatory networks essential for proper lineage specification and differentiation during pancreas development are reactivated or become deregulated in the context of cancer and exacerbate progression towards an aggressive phenotype. This review summarizes the recent literature on transcription factor networks and epigenetic gene regulation that play a crucial role during tumorigenesis.
format	article
author	Ruthger van Roey Thomas Brabletz Marc P. Stemmler Isabell Armstark
author_facet	Ruthger van Roey Thomas Brabletz Marc P. Stemmler Isabell Armstark
author_sort	Ruthger van Roey
title	Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
title_short	Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
title_full	Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
title_fullStr	Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
title_full_unstemmed	Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
title_sort	deregulation of transcription factor networks driving cell plasticity and metastasis in pancreatic cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ee2c60151b584f50933fbe927f90219c
work_keys_str_mv	AT ruthgervanroey deregulationoftranscriptionfactornetworksdrivingcellplasticityandmetastasisinpancreaticcancer AT thomasbrabletz deregulationoftranscriptionfactornetworksdrivingcellplasticityandmetastasisinpancreaticcancer AT marcpstemmler deregulationoftranscriptionfactornetworksdrivingcellplasticityandmetastasisinpancreaticcancer AT isabellarmstark deregulationoftranscriptionfactornetworksdrivingcellplasticityandmetastasisinpancreaticcancer
_version_	1718406598436585472

Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer

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