Expression and regulation of WNT5A and WNT5B in human cancer: Up-regulation of WNT5A by TNFα in MKN45 cells and up-regulation of WNT5B by β-estradiol in MCF-7 cells

Saitoh, Tetsuroh; Katoh, Masaru

doi:10.3892/ijmm.10.3.345

Cited by 43 publications

(38 citation statements)

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“…In contrast, down-regulation of Wnt5a in ATRA-treated mice may not involve the Shh pathway because the expression of genes other than Wnt5a and Axin2 are not altered. It is possible that RA directly regulates the expression of Wnt5a, as has been demonstrated in various tumor cell lines (36,37). This may correspond to some extent with the complex clinical spectrum of human anorectal malformations.…”

Section: Discussionmentioning

confidence: 99%

Induction of Wnt5a-Expressing Mesenchymal Cells Adjacent to the Cloacal Plate Is an Essential Process for Its Proximodistal Elongation and Subsequent Anorectal Development

et al. 2009

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Anorectal malformations encompass a broad spectrum of congenital defects and are related to the development of the genital tubercle, including the cloacal plate and urorectal septum. To explore the cellular and molecular basis of anorectal malformations, we analyzed the pathogenetic process using two mouse models: Danforth's short tail (Sd) and all-trans retinoic acid (ATRA)-treated mice. Embryologically, the cloacal plate may be divided into distal and proximal parts, with the distal part subdivided into ventral and dorsal parts. In the two mouse models, anorectal malformations occur due to improper development of the proximal part of the cloacal plate. At 10.5 days postcoitus (dpc), in Sd homozygotes, there was a lack of Shh expression only in the cloacal plate and the endoderm around the cloacal plate. In addition, Wnt5a was not expressed in the mesoderm adjacent to the cloacal plate in the two mouse models, and Axin2, which is regulated by Wnt signaling, was not expressed in the dorsal part of the cloacal plate at 12.5 dpc. Based on these results, we suggest that Wnt5a, which is downstream of Shh signaling, and Axin2 affect the development of the proximal part of the cloacal plate.

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Section: Discussionmentioning

confidence: 99%

Induction of Wnt5a-Expressing Mesenchymal Cells Adjacent to the Cloacal Plate Is an Essential Process for Its Proximodistal Elongation and Subsequent Anorectal Development

et al. 2009

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“…Recently, it has been shown that WNT5A and WNT10A expression in a gastric cancer cell line was promoted by TNF-␣. 29 To investigate whether the observed WNT5A expression was primarily due to a secondary effect mediated by an early autocrine action of TNF-␣, we cultivated human macrophages with TNF-␣ or mycobacteria in the presence or absence of inhibitory anti-TNF-␣ antibodies ( Figure 3D). Anti-TNF-␣ antibodies completely abrogated TNF-␣-induced WNT5A mRNA expression.…”

Section: Wnt5a Expression In Macrophages Is Mediated By Toll-like Recmentioning

confidence: 99%

The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation

Blumenthal

Ehlers

Lauber

et al. 2006

Blood

325

339

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IntroductionImmunity to infections depends on the successful integration of innate and adaptive defense strategies. 1 Cells of the innate immune system, such as macrophages and dendritic cells, recognize pathogen-associated molecular patterns shared by many microbes but not found in higher eukaryotes, via members of the Toll-like receptor (TLR) family. 2,3 TLR-dependent signaling pathways can directly induce macrophage antimicrobial programs but also initiate inflammatory cell recruitment and help prime cells of the adaptive immune system to amplify bactericidal effector mechanisms. Experimental infections with microorganisms have been used successfully to uncover the intricacies governing the interplay between innate and adaptive immunity. 4,5 For example, cell-wall components of Mycobacterium tuberculosis, the causative organism of tuberculosis, critically depend on TLR2 and TLR4 to induce secretion of the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣) and interleukin (IL-12, necessary for differentiating T-helper 1 cells). 6 Subsequently, mycobacteria-primed T cells secrete interferon gamma (IFN-␥) as a critical macrophageactivating agent. Eradication of mycobacteria is achieved only when both arms of the immune system are fine-tuned for full antimicrobial potency.Functionally, the Toll-mediated induction of antimicrobial effector systems is highly conserved between Drosophila melanogaster (D melanogaster) and Homo sapiens. 7,8 Another example for human evolutionarily ancient effector mechanisms is granulysin (a granule-stored bactericidal molecule), which is homologous to the amoebapores of Entamoeba histolytica. 9,10 Thus, there is ample precedence for evolutionarily conserved signatures governing individual facets of the immune response. To uncover novel regulatory pathways in innate responses to infection, we performed a microarray-based gene-expression screen with human macrophages infected with mycobacteria or conserved bacterial structures. We found mRNA for WNT5A, a homolog of Wingless in Drosophila species, to be consistently up-regulated in response to all stimuli.Wingless was originally characterized as a segment polarity gene in D melanogaster, which is essential in embryonic segmentation and patterning (reviewed in Klingensmith and Nusse 11 ). Various homologs of the Wingless protein, termed WNT, are involved in embryonic development of nonvertebrates and vertebrates, 12,13 where WNT signaling determines cell motility, differentiation, and apoptosis. 14 In mammalian hematopoiesis, WNT signaling is essential for stem-cell homeostasis 15 and lymphocyte differentiation. 16,17 Most recently, one member of the WNT family of proteins, WntD, was shown to be involved in regulating antibacterial defenses in Drosophila. 18 To date, however, WNT Center Borstel, Germany), phorbol-12-myristate13-acetate (PMA), calcium ionophore A23187 (both Sigma Aldrich, Taufkirchen, Germany), and phytohemagglutinin (PHA) were used for stimulation. To rule out the presence of lipopolysaccharides (LPSs) in the...

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“…[56][57][58] Upregulation of WNT5a has been identified in many different malignancies, including melanoma and carcinomas from the breast, esophagus, lung, pancreas, and stomach. [59][60][61][62][63] MMP1 was found to be the most overexpressed gene in squamous cell carcinoma in comparison with normal skin (FC ¼ 48.51; Table 2). MMP1 is one of the proteins of the matrix metalloproteinase family that are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling.…”

Section: P53 Signalingmentioning

confidence: 99%

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

Hui

Binder

2011

Modern Pathology

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Actinic keratosis is widely believed to be a neoplastic lesion and a precursor to invasive squamous cell carcinoma. However, there has been some debate as to whether actinic keratosis is in fact actually squamous cell carcinoma and should be treated as such. As the clinical management and prognosis of patients is widely held to be different for each of these lesions, our goal was to identify unique gene signatures using DNA microarrays to discriminate among normal skin, actinic keratosis, and squamous cell carcinoma, and examine the molecular pathways of carcinogenesis involved in the progression from normal skin to squamous cell carcinoma. Formalin-fixed and paraffin-embedded blocks of skin: five normal skins (pooled), six actinic keratoses, and six squamous cell carcinomas were retrieved. The RNA was extracted and amplified. The labeled targets were hybridized to the Affymetrix human U133plus2.0 array and the acquisition and initial quantification of array images were performed using the GCOS (Affymetrix). The subsequent data analyses were performed using DNA-Chip Analyzer and Partek Genomic Suite 6.4. Significant differential gene expression (42 fold change, Po0.05) was seen with 382 differentially expressed genes between squamous cell carcinoma and normal skin, 423 differentially expressed genes between actinic keratosis and normal skin, and 9 differentially expressed genes between actinic keratosis and squamous cell carcinoma. The differentially expressed genes offer the possibility of using DNA microarrays as a molecular diagnostic tool to distinguish between normal skin, actinic keratosis, and squamous cell carcinoma. In addition, the differentially expressed genes and their molecular pathways could be potentially used as prognostic markers or targets for future therapeutic innovations.

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Expression and regulation of WNT5A and WNT5B in human cancer: Up-regulation of WNT5A by TNFα in MKN45 cells and up-regulation of WNT5B by β-estradiol in MCF-7 cells

Cited by 43 publications

References 0 publications

Induction of Wnt5a-Expressing Mesenchymal Cells Adjacent to the Cloacal Plate Is an Essential Process for Its Proximodistal Elongation and Subsequent Anorectal Development

Induction of Wnt5a-Expressing Mesenchymal Cells Adjacent to the Cloacal Plate Is an Essential Process for Its Proximodistal Elongation and Subsequent Anorectal Development

The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

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