Functional and prognostic significance of the genomic amplification of frizzled 6 (<i>FZD6</i>) in breast cancer

Corda, Gabriele; Sala, Gianluca; Lattanzio, Rossano; Iezzi, Manuela; Sallese, Michele; Fragassi, Giorgia; Lamolinara, Alessia; Mirza, Hasan; Barcaroli, Daniela; Ermler, Sibylle; Silva, E; Yasaei, Hemad; Newbold, Robert F.; Vagnarelli, Paola; Mottolese, Marcella; Natali, Pier Giorgio; Perracchio, Letizia; Quist, Jelmar; Grigoriadis, Anita; Marra, Pierfrancesco; Tutt, Andrew N.J.; Piantelli, Mauro; Iacobelli, Stéfano; Laurenzi, Vincenzo De; Sala, Arturo

doi:10.1002/path.4841

Cited by 72 publications

(65 citation statements)

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“…We identified 448 differentially methylated genes (corresponding to 1269 probes) seem to have a role during early invasion represented by the Clark staging system (Table ). Of note, 18 out of the 385 genes in our data set show overlap with the TCGA data, of which several genes ( MECOM , CHD5 , TRIM55 , FZD6 , TPBG and TRPC4 ) were observed in association with invasion …”

Section: Resultsmentioning

confidence: 77%

DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Koroknai

Szász

Hernández-Vargas

et al. 2019

Experimental Dermatology

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Tumor cell invasion is one of the key processes during cancer progression, leading to life-threatening metastatic lesions in melanoma. As methylation of cancer-related genes plays a fundamental role during tumorigenesis and may lead to cellular plasticity which promotes invasion, our aim was to identify novel epigenetic markers on selected invasive melanoma cells. Using Illumina BeadChip assays and Affymetrix Human Gene 1.0 microarrays, we explored the DNA methylation landscape of selected invasive melanoma cells and examined the impact of DNA methylation on gene expression patterns. Our data revealed predominantly hypermethylated genes in the invasive cells affecting the neural crest differentiation pathway and regulation of the actin cytoskeleton. Integrative analysis of the methylation and gene expression profiles resulted in a cohort of hypermethylated genes (IL12RB2, LYPD6B, CHL1, SLC9A3, BAALC, FAM213A, SORCS1, GPR158, FBN1 and ADORA2B) with decreased expression. On the other hand, hypermethylation in the gene body of the EGFR and RBP4 genes was positively correlated with overexpression of the genes. We identified several methylation changes that can have role during melanoma progression, including hypermethylation of the promoter regions of the ARHGAP22 and NAV2 genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down-regulation of the methylcytosine dioxygenase TET2 gene, which regulates DNA methylation, was associated with hypermethylated promoter region of the gene. This can probably lead to the observed global hypermethylation pattern of invasive cells and might be one of the key changes during the development of malignant melanoma cells. K E Y W O R D S cell invasion, DNA methylation, gene body, malignant melanoma, TET2

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Section: Resultsmentioning

confidence: 77%

DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Koroknai

Szász

Hernández-Vargas

et al. 2019

Experimental Dermatology

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“…Wnt5a/5b and ROR1 are involved in breast cancer invasiveness and metastasis independent of β‐catenin signaling . FZD6 promotes TNBC cell motility and distant metastasis through the fibronectin‐actin axis . These studies indicate that noncanonical Wnt signaling is involved in basal‐like breast cancer/TNBC progression.…”

Section: Wnt Signaling Is Overactivated In Basal‐like Breast Cancer/tnbcmentioning

confidence: 76%

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

et al. 2018

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Wnt proteins, a group of secreted glycoproteins, mainly combine with receptors Frizzled (FZD) and/or low‐density‐lipoprotein receptor‐related proteins 5/6 (LRP5/6), initiating β‐catenin‐dependent and ‐independent signaling pathways. These pathways, which can be regulated by some secreted antagonists such as secreted Frizzled‐related proteins (SFRP) and dickkopf‐related protein (DKK), play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer. Wnt transgenic mice provide convincing evidence that Wnt signaling is involved in breast cancer initiation and progression, which is further strengthened by observations on human clinical breast cancer patients and studies on in vitro cultured human breast cancer cells. This review focuses on the roles of Wnt ligands, receptors and antagonists in breast cancer development instead of molecules or signaling transactivating β‐catenin independent on Wnt upstream components.

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“…Earlier studies have demonstrated the involvement of several Frizzled receptors, including FZD8, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, and FZD10 in different cancers. Though Frizzled receptors function as key components of the Wnt signaling pathway, the specific link with the ETS‐related transcription factor ERG is unknown.…”

Section: Discussionmentioning

confidence: 99%

Wnt receptor Frizzled 8 is a target of ERG in prostate cancer

et al. 2018

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Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overexpression of ERG in the majority of prostate cancers. Overexpression of ERG plays a critical role in prostate oncogenesis and development of metastatic disease. Among the downstream effectors of ERG, Frizzled family member FZD4 has been shown to be a target of ERG. Frizzled-8 (FZD8) has been shown to be involved in PCa bone metastasis. In the present study, we show that the expression of FZD8 is directly correlated with ERG expression in PCa. Furthermore, we show that ERG directly targets and activates FZD8 by binding to its promoter. This activation is specific to ETS transcription factor ERG and not ETV1. We propose that ERG overexpression in PCa leads to induction of Frizzled family member FZD8, which is known to activate the Wnt pathway. Taken together, these findings uncover a novel mechanism for PCa metastasis, and indicate that FZD8 may represent a potential therapeutic target for PCa.

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Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer

Cited by 72 publications

References 50 publications

DNA hypermethylation is associated with invasive phenotype of malignant melanoma

DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

Wnt receptor Frizzled 8 is a target of ERG in prostate cancer

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