Frizzled homolog proteins, microRNAs and Wnt signaling in cancer

Abstract

Wnt signaling pathways play important roles in tumorigenesis and are initiated by binding of Wnt to various receptors including frizzleds (FZDs). FZDs are one of several families of receptors comprised of FZD/LRP/ROR2/RYK in the Wnt signaling pathway. Expression of some FZD receptors are up-regulated, thereby activating the Wnt signaling pathway and is correlated with cancer malignancy and patient outcomes (recurrence and survival) in many cancers. The FZD family contains ten genes in humans and their function has not been completely examined including the regulatory mechanisms of FZD genes in cancer. Knockdown of FZDs may suppress the Wnt signaling pathway resulting in decreased cell growth, invasion, motility and metastasis of cancer cells. Recently a number of microRNAs (miRNAs) have been identified and reported to be important in several cancers. MiRNAs regulate target gene expression at both the transcription and translation levels. The study of miRNA is a newly emerging field and promises to be helpful in understanding the pathogenesis of FZDs in cancer. Also miRNAs may be useful in regulating FZDs in cancer cells. Therefore the aim of this review is to discuss current knowledge of the functional mechanisms of FZDs in cancer, including regulation by miRNAs and the potential for possible use of miRNAs and FZDs in future clinical applications.

Interplay between microRNAs and WNT/β-catenin signalling pathway regulates epithelial–mesenchymal transition in cancer

“…FZDs have been identified as seven transmembrane receptors of the WNT ligands, which transduce the signals of canonical and non-canonical WNT signalling [105]. In VCaP prostate cancer cells with TMPRSS2-ERG gene fusion and invasive U87R4 glioma cell line, FZD4 induced WNT/b-catenin signalling activation, loss of E-cadherin and overexpression of Snail1 [106,107].…”

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…Moreover, also in Chinese patients, the survival analyses results showed that patients with high expression levels of hsa-miR-335 had reduced overall survival rate and high recurrence risk of gastric cancer [166] . Among hsamiR-335 targeted genes is Fzd-3, a member of the FZD receptor family, upregulated in several cancers [167] . Metastatic potential of gastric cancer cells have been associated with changes in the expression profile of miRNAs involved in regulating Wnt signaling pathway.…”

Characterization of drug-induced splicing complexity in prostate cancer cell line using long read technology

“…We observed key oncogenic protein domains (families) frequently found in DMSO but not in treatment, such as histone deacetylase interacting, PI3-kinase, p85-and Ras binding domains and DNA polymerase A/B families. Notably frizzled protein, which activates the Wnt pathway is ranked as the top DMSO-unique proteins [20]. A full list of condition specific domain annotation is shown in Table S1.…”