Tumor cell heterogeneity and its transcriptional bases in pancreatic cancer: a tale of two cell types and their many variants

Review12 April 2021 Tumor cell heterogeneity and its transcriptional bases in pancreatic cancer: a tale of two cell types and their many variants Marta Milan Corresponding Author Marta Milan [email protected] orcid.org/0000-0003-1231-0586 Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy Search for more papers by this author Giuseppe R Diaferia Corresponding Author Giuseppe R Diaferia [email protected] orcid.org/0000-0003-4022-8483 Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy Search for more papers by this author Gioacchino Natoli Corresponding Author Gioacchino Natoli [email protected] orcid.org/0000-0003-0711-2411 Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy Humanitas University, Milan, Italy Search for more papers by this author Marta Milan Corresponding Author Marta Milan [email protected] orcid.org/0000-0003-1231-0586 Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy Search for more papers by this author Giuseppe R Diaferia Corresponding Author Giuseppe R Diaferia [email protected] orcid.org/0000-0003-4022-8483 Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy Search for more papers by this author Gioacchino Natoli Corresponding Author Gioacchino Natoli [email protected] orcid.org/0000-0003-0711-2411 Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy Humanitas University, Milan, Italy Search for more papers by this author Author Information Marta Milan *,1,3, Giuseppe R Diaferia *,1 and Gioacchino Natoli *,1,2 1Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy 2Humanitas University, Milan, Italy 3Present address: The Francis Crick Institute, London, UK *Corresponding author. Tel: +44 20 37965523; E-mail: [email protected] *Corresponding author. Tel: +39 02 57485054; E-mail: [email protected] *Corresponding author. Tel: +39 02 57489953; E-mail: [email protected] The EMBO Journal (2021)40:e107206https://doi.org/10.15252/embj.2020107206 This article is part of the Cancer Reviews 2021 series. Full textView the full text of the articlePDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Pancreatic ductal adenocarcinoma (PDAC), one of the most highly lethal tumors, is characterized by complex histology, with a massive fibrotic stroma in which both pseudo-glandular structures and compact nests of abnormally differentiated tumor cells are embedded, in different proportions and with different mutual relationships in space. This complexity and the heterogeneity of the tumor component have hindered the development of a broadly accepted, clinically actionable classification of PDACs, either on a morphological or a molecular basis. Here, we discuss evidence suggesting that such heterogeneity can to a large extent, albeit not exclusively, be traced back to two main classes of PDAC cells that commonly coexist in the same tumor: cells that maintained their ability to differentiate toward endodermal, mucin-producing epithelia and epithelial cells unable to form glandular structures and instead characterized by various levels of squamous differentiation and the expression of mesenchymal lineage genes. The underlying gene regulatory networks and how they are controlled by distinct transcription factors, as well as the practical implications of these two different populations of tumor cells, are discussed. Next ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 40,Issue 13,01 July 2021This month's cover highlights the article Expression of human-specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility by Lei Xing, Wieland B. Huttner and colleagues. This study reports on the novel tumor promoting succinyltransferase function of HAT1, in addition to its acetyltransferase activity. The cover shows HAT1 as a machine that transfers different caps (acetylation or succinylation) to its target proteins (robots) on the conveyor belt. (Cover concept by the authors. Cover illustration by SciStories LLC (scistories.com).) Volume 40Issue 131 July 2021In this issue RelatedDetailsLoading ...