Disease relevance of WNT5A

• Both WNT5A and FZD5 also were detected in granulomatous lesions in the lungs of Mycobacterium tuberculosis-infected patients [1].
• We have also reported frequent up-regulation of WNT2 and WNT5A in primary gastric cancer, which is probably due to cancer-stromal interaction [2].
• Among 7 pancreatic cancer cell lines, WNT5A was up-regulated in Hs700T, and WNT5B in PANC-1 [2].
• WNT5B, but not WNT5A, was up-regulated by beta-estradiol in MCF-7 cells derived from breast cancer [2].
• WNT5A was relatively highly expressed in TE6 and TE10 among 12 esophageal cancer cell lines, and WNT5B was expressed in the majority of esophageal cancer cell lines [2].
• Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome [3].

High impact information on WNT5A

• The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation [1].
• Microarray--assisted gene--expression screens of human macrophages revealed WNT5A, a homolog of Wingless, a key regulator of Drosophila melanogaster embryonic segmentation and patterning, to be consistently up-regulated following stimulation with different mycobacterial species and conserved bacterial structures [1].
• Functional studies showed that WNT5A and FZD5 regulate the microbially induced interleukin-12 response of antigen-presenting cells and interferon-gamma production by mycobacterial antigen-stimulated T cells [1].
• The results are applied to a family of Boolean networks derived from gene-expression data collected in a study of metastatic melanoma, the intent being to devise a control strategy that reduces the WNT5A gene's action in affecting biological regulation [4].
• Previous studies have shown that three members of the Wnt signaling pathway, the ligand WNT5A, the receptor FZ4, and the Wnt antagonist FRZB1, are implicated in the formation and differentiation of the digits [5].

Biological context of WNT5A

• FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology [6].
• Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21 [7].
• WNT5A gene at chromosome 3p14.3 and WNT5B gene at chromosome 12p13.33 are paralogs within the human genome [8].

Anatomical context of WNT5A

• WNT5A and WNT5B were expressed together in 5 embryonal tumor cell lines, and were slightly down-regulated by all-trans retinoic acid in NT2 cells [2].
• WNT5A then activates canonical WNT signaling in epithelial cells [9].
• Oncogenic WNT5A activates canonical WNT signaling in cancer stem cells for self-renewal, and non-canonical WNT signaling at the tumor-stromal interface for invasion and metastasis [9].
• WNT5A mRNA was relatively highly expressed in salivary gland, bladder, uterus, placenta, and fetal kidney [10].
• IL6-induced WNT5A activates canonical WNT signaling for autocrine proliferation of human synovial fibroblasts in rheumatoid arthritis [9].

Associations of WNT5A with chemical compounds

• Furthermore, we detected an increase of WNT5A protein in the medium by DHT and inhibition of the increase by BMP-2 [11].

Regulatory relationships of WNT5A

• STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer (Review) [9].

Other interactions of WNT5A

• Here, WNT5A was characterized as the evolutionarily conserved target of the STAT3 signaling cascade based on 11-bp-spaced tandem STAT3-binding sites within intron 4 of human, chimpanzee, cow, mouse and rat WNT5A orthologs [9].
• It is noteworthy that all six Wnt ligands that are overexpressed in malignant cell lines are known to signal through the canonical Wnt/beta-catenin signaling pathway, whereas down-regulated WNT5A and WNT5B ligands signal via the non-canonical pathway [12].
• CONCLUSIONS: Early induction of WNT5A, coupled with the coordinated induction and repression of genes that modulate the Wnt signaling pathway, led to the early, selective induction of WISP1 and no other Wnt-inducible genes [13].
• SNP of genes encoding components of the cytokine-induced WNT5A signaling loop is a predicted risk factor for RA and cancer, especially diffuse-type gastric and pancreatic cancer [9].
• The recent development of high-throughput technologies aimed at global molecular profiling of cancer is switching on the spotlight at previously unknown candidate genes involved in melanoma, such as WNT5A and BRAF [14].

Analytical, diagnostic and therapeutic context of WNT5A

• Finally, using a combination of Southern blotting, PCR amplification, and in situ hybridization, the human Wnt-5A (WNT5A) gene was mapped to chromosome 3p14-p21 [7].

References