DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment

Autor: Mathot, P, Grandin, M, Devailly, G, Souazé, Frédérique, Cahais, V., Moran, S., Campone, Mario, Herceg, Z, Esteller, M, Juin, Philippe, Mehlen, Patrick, Dante, R
Přispěvatelé: Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Developmental Biology [Midlothian, UK], University of Edinburgh-The Roslin Institute, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Epigenetics Group [Lyon], International Agency for Cancer Research (IACR), Cancer Epigenetics and Biology Program-PEBC [Barcelone, Spain], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Physiological Sciences Department [Barcelona, Spain], Institució Catalana de Recerca i Estudis Avançats (ICREA)-School of Medicine and Health Sciences [Barcelona, Spain]-University of Barcelona - UB [Spain], PM and GD are recipients of the fellowship from the Ligue Nationale contre le Cancer. MG is a recipient of the fellowship from the Fondation ARC pour la Recherche sur le Cancer and LabExDEVwe-CAN. We acknowledge Integragen for library preparations and highthrouput sequencing experiments The present work was supported by Ligue Contre le Cancer (EL2015.LNCC), Institut National Du Cancer (2011–143 and 2016–166), European Research Council (294079), Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, University of Lyon, and Centre Léon Bérard., Université de Lyon (COMUE), Universitat de Barcelona, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology and Biological Sciences Research Council (BBSRC)-Biotechnology and Biological Sciences Research Council (BBSRC), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Oncogenesis
Oncogenesis, Nature Publishing Group: Open Access Journals-Option C, 2017, 6 (10), pp.e390. ⟨10.1038/oncsis.2017.88⟩
Oncogenesis, Nature Publishing Group: Open Access Journals-Option C, 2017, 6 (10), pp.e390-e390. ⟨10.1038/oncsis.2017.88⟩
Dipòsit Digital de la UB
Universidad de Barcelona
Oncogenesis 10 (6), Non Paginé. (2017)
Mathot, P, Grandin, M, Devailly, G, Souaze, F, Cahais, V, Moran, S, Campone, M, Herceg, Z, Esteller, M, Juin, P, Mehlen, P & Dante, R 2017, ' DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment ', Oncogenesis, vol. 6, no. 10, e390 . https://doi.org/10.1038/oncsis.2017.88
Recercat. Dipósit de la Recerca de Catalunya
instname
Oncogenesis, 2017, 6 (10), pp.e390. ⟨10.1038/oncsis.2017.88⟩
ISSN: 2157-9024
Popis: International audience; Breast cancer-associated fibroblasts (CAFs) have a crucial role in tumor initiation, metastasis and therapeutic resistance by secreting various growth factors, cytokines, protease and extracellular matrix components. Soluble factors secreted by CAFs are involved in many pathways including inflammation, metabolism, proliferation and epigenetic modulation, suggesting that CAF-dependent reprograming of cancer cells affects a large set of genes. This paracrine signaling has an important role in tumor progression, thus deciphering some of these processes could lead to relevant discoveries with subsequent clinical implications. Here, we investigated the mechanisms underlying the changes in gene expression patterns associated with the cross-talk between breast cancer cells and the stroma. From RNAseq data obtained from breast cancer cell lines grown in presence of CAF-secreted factors, we identified 372 upregulated genes, exhibiting an expression level positively correlated with the stromal content of breast cancer specimens. Furthermore, we observed that gene expression changes were not mediated through significant DNA methylation changes. Nevertheless, CAF-secreted factors but also stromal content of the tumors remarkably activated specific genes characterized by a DNA methylation pattern: hypermethylation at transcription start site and shore regions. Experimental approaches (inhibition of DNA methylation, knockdown of methyl-CpG-binding domain protein 2 and chromatin immunoprecipitation assays) indicated that this set of genes was epigenetically controlled. These data elucidate the importance of epigenetics marks in the cancer cell reprogramming induced by stromal cell and indicated that the interpreters of the DNA methylation signal have a major role in the response of the cancer cells to the microenvironment.
Databáze: OpenAIRE
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