Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts

Vizoso, Miguel; Puig, Marta; Carmona, Francisco javier García; Maqueda, María; Velásquez, Adriana; Gómez, Antonio; Labernadie, Anna; Lugo, Roberto; Gabasa, Marta; Rigat-Brugarolas, Luis G.; Trepat, Xavier; Ramírez, Josep; Morán, Sebastian; Vidal, Enrique; Reguart, Noemı́; Perera, Alexandre; Esteller, Manel; Alcaraz, Jordi

doi:10.1093/carcin/bgv146

Cited by 84 publications

(120 citation statements)

References 52 publications

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“…Notably, we found no evidence of the global hypomethylation that typically occurs in tumor epithelial cells (Supplemental Fig. S1E,F) and as previously reported for CAFs from gastric and non-small cell lung cancers (Jiang et al 2008;Vizoso et al 2015).…”

Section: Bph-1+npfsupporting

confidence: 82%

“…Here we ask if genome-wide differences in the epigenome underpin the persistent phenotypic differences between CAFs and NPFs. Earlier studies using low-resolution techniques found examples of DNA methylation changes in CAFs or tumor stroma from various cancer types (Hu et al 2005;Fiegl et al 2006;Hanson et al 2006;Rodriguez-Canales et al 2007;Dawsey et al 2008;Jiang et al 2008;Banerjee et al 2014;Vizoso et al 2015). However, the full epigenome landscape of CAFs remains uncharted, so the precise epigenetic changes and their contribution to altered transcriptional patterns is unknown.…”

Section: Australiamentioning

confidence: 99%

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Enduring epigenetic landmarks define the cancer microenvironment

et al. 2018

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The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples.

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Section: Bph-1+npfsupporting

confidence: 82%

Section: Australiamentioning

confidence: 99%

Enduring epigenetic landmarks define the cancer microenvironment

et al. 2018

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“…These hypermethylated genes (homeobox A9 (HOXA9) and HOXB6) were independently validated by bisulfite sequencing. Genome-wide human methylation microarray analysis was conducted on CAFs and paired control fibroblasts from non-small cell lung cancer patients by Vizoso et al (2015). Compared with normal fibroblasts, they found global DNA hypomethylation in CAFs accompanied by some hypermethylated genes.…”

Section: Dna Methylation In Cancer-associated Fibroblastsmentioning

confidence: 99%

“…CAFs were shown to promote tumor progression and invasion through secreting the protumoral growth factor IGF-1 (Mueller and Fusenig, 2004;Ahmed and Farquharson, 2010). Vizoso et al (2015) identified hypermethylationassociated SMAD family member 3 (SMAD3) silencing in CAFs, which was associated with aberrant response to exogenous TGF-β1. Exogenous TGF-β1 can induce contractility and ECM expression in CAFs, but not in normal fibroblasts, suggesting that SMAD3 silencing promotes hyperresponsiveness to TGF-β in CAFs.…”

Section: Dna Methylation In Cancer-associated Fibroblastsmentioning

confidence: 99%

DNA methylation in the tumor microenvironment

Zhang

Fujiwara

Che

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumorassociated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.

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“…Thus, regardless of the initiating insult, myofibroblasts share common markers like the fibroblast-activation protein and α-smooth muscle protein and, importantly, maintain a stable phenotype when severed from the cellular source of their generation (12,13). This phenotypic durability relies on the reprogramming of their epigenetic landscape (11,(14)(15)(16)(17), a well attested genomic signature in CAFs (18)(19)(20)(21).…”

Section: The Myofibroblast In Cancer Stroma and In Non-neoplastic Chrmentioning

confidence: 99%

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling

Shany

Sigal-Batikoff

Lamprecht

2016

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As mentioned briefly above, one of the principal steps whereby normal stromal fibroblasts acquire the CAF phenotype is their trans-differentiation to myofibroblasts. Notably, we and others (10, 11) have been impressed by the striking similarity in biological behavior and function of the myofibroblast in neoplasia and in a vast range of nonneoplastic chronic diseases that are characterized by extensive 6225 Τhis article is freely accessible online.

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Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts

Abstract: SummaryDNA methylation profiling of TAFs reveals global demethylation and a selective impact on the TGF-β pathway. Moreover, it suggests the fibrocyte origin of a fraction of TAFs, and identifies a novel prognostic biomarker in non-small cell lung cancer.

Cited by 84 publications

References 52 publications

Enduring epigenetic landmarks define the cancer microenvironment

Enduring epigenetic landmarks define the cancer microenvironment

DNA methylation in the tumor microenvironment

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling

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