Wnt Signaling in the Breast: From Development to Disease

Oliveira, Willy Antoni Abreu de; Laithy, Youssef El; Bruna, Alejandra; Annibali, Daniela; Lluı́s, Frederic

doi:10.3389/fcell.2022.884467

Cited by 12 publications

(14 citation statements)

References 168 publications

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“…Aberrant Wnt signaling plays a critical role in mammary gland development and breast tumorigenesis [ 22 , 23 ]. STAT3 signaling possesses multifaceted functions in the immune response in the breast tumor microenvironment and has downstream target genes that overlap with the Wnt signaling pathway [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

High-Fat Diet Exposure in Early Life Alters Mammary Metabolic and Inflammatory Microenvironment in Favor of Breast Tumorigenesis Later in Life in Mice

et al. 2023

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Emerging evidence highlights the important impact of early-life exposures on cancer development later in life. The present study aimed to investigate the impacts of a high-fat diet in early life on the mammary microenvironment in relation to breast tumorigenesis. Forty-four female C57BL/6 mice were fed a low-fat diet (LF, 10 kcal% fat) or a high-fat diet (HF, 60 kcal% fat) for 8 weeks starting at ~4 weeks of age. Twenty-two mice were sacrificed immediately after an 8 week feeding, and the rest of mice were switched to a normal diet for maintenance (Lab Diet, #5P76) for additional 12 weeks. A panel of metabolic parameters, inflammatory cytokines, as well as tumorigenic Wnt-signaling target genes were analyzed. The HF diet increased body weight and exacerbated mammary metabolic and inflammatory status. The disrupted microenvironment remains significant to the later life equivalent to young adulthood (p < 0.05). Mammary Wnt-signaling was elevated right after the HF diet as indicated by the upregulated expression of its downstream genes, whereas it was surprisingly suppressed after switching diets (p < 0.05). In summary, HF-induced overweight/obesity in early life altered the mammary metabolic and inflammatory microenvironments in favor of breast tumorigenesis, although its overall impact to breast cancer later in life warrants further investigation.

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Section: Resultsmentioning

confidence: 99%

High-Fat Diet Exposure in Early Life Alters Mammary Metabolic and Inflammatory Microenvironment in Favor of Breast Tumorigenesis Later in Life in Mice

et al. 2023

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“…Importantly, evaluating prognosis and monitoring tumor response in real time during treatment continues to be an unmet clinical need in advanced BC ( Gupta et al, 2020 ). Wnt signaling is a very relevant pathway in BC whose molecular alterations have clinical implications to establish the prognosis of the disease ( Mukherjee et al, 2012 ) and has been associated to breast cancer therapy response ( Abreu de Oliveira et al, 2022 ). Therefore, it would be interesting to evaluate in future studies whether the hypermethylation of WNT1 could be useful for the selection of patients susceptible to systemic therapies (CDK inhibitors for example) in the BC metastatic setting.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer

Rodríguez‐Casanova

Costa-Fraga²,

Castro-Carballeira³

et al. 2022

Front. Cell Dev. Biol.

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Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients using an epigenomic approach to discover potential noninvasive biomarkers. Plasma cfDNA was analyzed using the Infinium MethylationEpic array in a cohort of 14 women, including metastatic LBBC patients and nontumor controls. The methylation levels of cfDNA and tissue samples were validated with droplet digital PCR. The methylation and gene expression data of 582 primary luminal breast tumors and 79 nontumor tissues were obtained from The Cancer Genome Atlas (TCGA). We found an episignature of 1,467 differentially methylated CpGs that clearly identified patients with LBBC. Among the genes identified, the promoter hypermethylation of WNT1 was validated in cfDNA, showing an area under the ROC curve (AUC) of 0.86 for the noninvasive detection of metastatic LBBC. Both paired cfDNA and primary/metastatic breast tumor samples showed hypermethylation of WNT1. TCGA analysis revealed significant WNT1 hypermethylation in the primary tumors of luminal breast cancer patients, with a negative association between WNT1 methylation and gene expression. In this proof-of-principle study, we discovered an episignature associated with metastatic LBBC using a genome-wide cfDNA methylation approach. We also identified the promoter hypermethylation of WNT1 in cfDNA as a potential noninvasive biomarker for luminal breast cancer. Our results support the use of EPIC arrays to identify new epigenetic noninvasive biomarkers in breast cancer.

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“…Other reports showed that during development components of the FGF, Wnt, Notch, BPM, and Hedgehog signaling orchestrate crucial cellular events including proliferation, migration, differentiation, epithelial-mesenchymal transition (EMT), morphogenesis and somite myogenesis patterning. When gene expression controlling these events is dysregulated, it leads to disease induction ( Hansson et al, 2004 ; Logan and Nusse, 2004 ; Ma et al, 2010 ; Teven et al, 2014 ; Xiao et al, 2017 ; Abreu de Oliveira et al, 2022 ; Alrefaei and Abu-Elmagd, 2022 ; Towler and Shore, 2022 ). Although our RT did not receive microRNA-related manuscripts, it is well-established that microRNAs play an important role in physiology and disease ( Sayed and Abdellatif, 2011 ; Bhaskaran and Mohan, 2014 ; Kalayinia et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Editorial: Advances in genomic and genetic tools, and their applications for understanding embryonic development and human diseases

Abu‐Elmagd

Assidi

Alrefaei

et al. 2022

Front. Cell Dev. Biol.

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Significant advances have been recently made in the development of the genetic and genomic platforms. This has greatly contributed to a better understanding of gene expression and regulation machinery. Consequently, this led to considerable progress in unraveling evidence of the genotype-phenotype correlation between normal/abnormal embryonic development and human disease complexity. For example, advanced genomic tools such as next-generation sequencing, and microarray-based CGH have substantially helped in the identification of gene and copy number variants associated with diseases as well as in the discovery of causal gene mutations. In addition, bioinformatic analysis tools of genome annotation and comparison have greatly aided in data analysis for the interpretation of the genetic variants at the individual level. This has unlocked potential possibilities for real advances toward new therapies in personalized medicine for the targeted treatment of human diseases. However, each of these genomic and bioinformatics tools has its limitations and hence further efforts are required to implement novel approaches to overcome these limitations. It could be possible that the use of more than one platform for genotype-phenotype deep analysis is an effective approach to disentangling the cause and treatment of the disease complexities. Our research topic aimed at deciphering these complexities by shedding some light on the recent applications of the basic and advanced genetic/genomic and bioinformatics approaches. These include studying gene-gene, protein-protein, and gene-environment interactions. We, in addition, aimed at a better understanding of the link between normal/abnormal embryonic development and the cause of human disease induction.

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Wnt Signaling in the Breast: From Development to Disease

Cited by 12 publications

References 168 publications

High-Fat Diet Exposure in Early Life Alters Mammary Metabolic and Inflammatory Microenvironment in Favor of Breast Tumorigenesis Later in Life in Mice

High-Fat Diet Exposure in Early Life Alters Mammary Metabolic and Inflammatory Microenvironment in Favor of Breast Tumorigenesis Later in Life in Mice

A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer

Editorial: Advances in genomic and genetic tools, and their applications for understanding embryonic development and human diseases

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