Methylation status of the promoter region of the human frizzled 9 gene in acute myeloid leukemia

Zhang, Yingjie; Jiang, Qi; Kong, Xiaolin; Yang, Lili; Hu, Wanzhen; Lv, Chengfang; Li, Yinghua

doi:10.3892/mmr.2016.5387

Cited by 9 publications

(7 citation statements)

References 32 publications

(34 reference statements)

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“…Additionally, FZD9 has an essential role in osteoblast differentiation for bone formation and pre-B cell development [127]. FZD9 has been studied in multiple cancers including NSCLC, astrocytoma, osteosarcoma, AML, and hepatocellular carcinoma (HCC) [96][97][98][99]127]. FZD9 interacts with several WNT ligands including WNT2, WNT5a, and WNT3a depending on the tumor; these interactions promote EMT and invasiveness.…”

Section: Frizzledmentioning

confidence: 99%

Cancer chemoprevention through Frizzled receptors and EMT

et al. 2021

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Frizzled (FZD) transmembrane receptors are well known for their role in β-catenin signaling and development and now understanding of their role in the context of cancer is growing. FZDs are often associated with the process of epithelial to mesenchymal transition (EMT) through β-catenin, but some also influence EMT through non-canonical pathways. With ten different FZDs, there is a wide range of activity from oncogenic to tumor suppressive depending on the tissue context. Alterations in FZD signaling can occur during development of premalignant lesions, supporting their potential as targets of chemoprevention agents. Agonizing or antagonizing FZD activity may affect EMT, which is a key process in lesion progression often targeted by chemoprevention agents. Recent studies identified a specific FZD as important for activity of an EMT inhibiting chemopreventive agent and other studies have highlighted the previously unrecognized potential for targeting small molecules to FZD receptors. This work demonstrates the value of investigating FZDs in chemoprevention and here we provide a review of FZDs in cancer EMT and their potential as chemoprevention targets.

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Section: Frizzledmentioning

confidence: 99%

Cancer chemoprevention through Frizzled receptors and EMT

et al. 2021

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“…However, FZD9 was downregulated in acute myeloid leukemia due to the promoter methylation, suggesting it may also function as a tumor suppressor [ 73 ]. It has been reported that the direct interaction of WNT7a ligand and its receptor FZD9 repressed cell growth and promoted cell differentiation in NSCLC, indicating an antitumor effect of WNT7a and FZD9 in human cancers [ 74 , 75 ].…”

Section: Biological Functions and Mechanismmentioning

confidence: 99%

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Zeng

Chen

2018

IJMS

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Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

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“…These observations are consistent with a loss of HSPCs during development. Furthermore, disruption of FZD9 expression has been linked to hematological malignancies, highlighting its importance in human hematopoietic cells as well (Jiang et al, 2009;Martin-Subero et al, 2009;Zhang et al, 2016). For instance, FZD9 was identified as one of 6 genes most frequently hypermethylated in hematological neoplasms (Martin-Subero et al, 2009).…”

Section: Egfr and Fzd9b Are Required For The Wnt9a Signal In Vitro Anmentioning

confidence: 99%

EGFR confers exquisite specificity of Wnt9a-Fzd9b signaling in hematopoietic stem cell development

Grainger

Nguyen

Richter

et al. 2018

Preprint

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SummaryThe mechanisms of Wnt-Frizzled (Fzd) signaling selectivity and their biological implications remain unclear. We demonstrate for the first time that the epidermal growth factor receptor (EGFR) is required as a co-factor for Wnt signaling. Using genetic studies in zebrafish, paired with in vitro cell biology and biochemistry, we have determined that Fzd9b signals specifically with Wnt9a in vivo and in vitro to elicit β-catenin dependent Wnt signals that regulate hematopoietic stem and progenitor cell (HSPC) development in the dorsal aorta. This requirement is conserved in the derivation of HSPCs from human embryonic stem cells. Wnt9a-Fzd9b specificity requires two intracellular domains in Fzd9b, which interact with EGFR as a required co-factor to promote signal transduction. EGFR phosphorylates one tyrosine residue on Fzd9b, a requirement for the Wnt signal. These findings indicate that Wnt signaling interactions can be exquisitely specific and inform protocols for derivation of HSPCs in vitro.HighlightsAn in vitro signaling screen identifies Fzd9b as a Wnt9a-specific receptor.Fzd9b and Wnt9a regulate hematopoietic stem cell development as a cognate pair.WNT9A and FZD9 are required for HSPC derivation from human pluripotent cells in vitro.EGFR confers specificity to Wnt9a-Fzd9b signaling in zebrafish and human cells.

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Methylation status of the promoter region of the human frizzled 9 gene in acute myeloid leukemia

Cited by 9 publications

References 32 publications

Cancer chemoprevention through Frizzled receptors and EMT

Cancer chemoprevention through Frizzled receptors and EMT

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

EGFR confers exquisite specificity of Wnt9a-Fzd9b signaling in hematopoietic stem cell development

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