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Title: DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment
Author: Mathot, Pauline
Grandin, Mélodie
Devailly, Guillaume
Souazé, Frédérique
Cahais, Vincent
Moran, Sebastian
Campone, Mario
Herceg, Zdenko
Esteller, Manel
Juin, Philippe P.
Mehlen, Patrick
Dante, Robert
Keywords: ADN
Cèl·lules canceroses
Càncer de mama
Cancer cells
Breast cancer
Issue Date: 23-Oct-2017
Publisher: Nature Publishing Group
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Oncogenesis, 2017, vol. 6, num. 10, p. e390
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ISSN: 2157-9024
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)
Publicacions de projectes de recerca finançats per la UE

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