Structure, Expression and Chromosome Mapping of <i>MLZE</i>, a Novel Gene Which Is Preferentially Expressed in Metastatic Melanoma Cells

Watabe, Kenji; Ito, Akihiko; Asada, Hideo; Endo, Yuichi; Kobayashi, Toshiko; Nakamoto, Ken'i; Itami, Satoshi; Takao, Sonshin; Shinomura, Yasuhisa; Aikou, Takashi; Yoshikawa, Kunihiko; Matsuzawa, Yūji; Kitamura, Yukihiko; Nishimura, Hiroshi

doi:10.1111/j.1349-7006.2001.tb01076.x

Cited by 91 publications

(90 citation statements)

References 25 publications

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“…Among the most highly significant genes elevated by WNT3A (Fig. 4B) are Axin2 (35) and Tcf7 (37), which are direct targets of Wnt/ß-catenin signaling; Mme and Mlze, down-regulated genes previously linked to melanoma progression (38,39); Mitf, which is linked to pigment cell fate; and Trpm1, Met, Sox9, and Kit, which are highly expressed during melanocyte and neural crest development (40). The complete list of significantly regulated genes is presented in Dataset S1.…”

Section: Activation Of Wnt/ß-catenin Signaling Is Correlated With Decmentioning

confidence: 99%

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Chien

Moore

Lonsdorf

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

317

319

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This study demonstrates that in malignant melanoma, elevated levels of nuclear ß-catenin in both primary tumors and metastases correlate with reduced expression of a marker of proliferation and with improved survival, in contrast to colorectal cancer. The reduction in proliferation observed in vivo is recapitulated in B16 murine melanoma cells and in human melanoma cell lines cultured in vitro with either WNT3A or small-molecule activators of ß-catenin signaling. Consistent with these results, B16 melanoma cells expressing WNT3A also exhibit decreased tumor size and decreased metastasis when implanted into mice. Genome-wide transcriptional profiling reveals that WNT3A up-regulates genes implicated in melanocyte differentiation, several of which are down-regulated with melanoma progression. These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/ß-catenin signaling in normal melanocyte development, thereby altering melanoma cell fate to one that may be less proliferative and potentially less aggressive. Our results may explain the observed loss of nuclear ß-catenin with melanoma progression in human tumors, which could reflect a dysregulation of cellular differentiation through a loss of homeostatic Wnt/ß-catenin signaling.differentiation ͉ prognosis ͉ metastasis ͉ WNT5A ͉ B16 model ͉ microarray M alignant melanoma accounts for Ͻ5% of all skin cancers, yet is responsible for 80% of skin cancer deaths (1). The outlook for patients with metastatic melanoma remains quite bleak, with a 5-year survival rate of only 5%-15% that has not changed significantly over decades despite intensive efforts to develop an effective therapy. Although the molecular mechanisms underlying the formation and progression of melanoma remain unresolved, recent studies have implicated Wnt signal transduction pathways in melanoma biology (2), raising the question of whether this insight can be used to develop a therapy.

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Section: Activation Of Wnt/ß-catenin Signaling Is Correlated With Decmentioning

confidence: 99%

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Chien

Moore

Lonsdorf

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

317

319

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“…Based on the differential protein expressions in gastric and esophageal cancers, human GSDMA, GSDMC, and GSDMD are considered tumor suppressors whereas an overexpression of GSDMB in gastric, uterine cervix, and breast cancers was accompanied by tumor progression and metastasis (3)(4)(5)(6)(7)(8). The overexpression of GSDMC in metastatic melanoma cells is an exception to its apoptotic role (9). In addition to cancer, genome-wide association studies (GWAS) have revealed a correlation between single nucleotide polymorphisms (SNPs) in both the protein coding and transcriptional regulatory regions of the neighboring genes GSDMA, GSDMB, and ORDML3 in the 17q12.2.1 loci and susceptibility to diseases such as asthma (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), type 1 diabetes (21,22), Crohn's disease, ulcerative colitis (22,23), and rheumatoid arteritis (22,24).…”

mentioning

confidence: 99%

Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein

Chao

Kulakova

Herzberg

2017

Proc. Natl. Acad. Sci. U.S.A.

145

189

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The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N-and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at 88 DNVD 91 within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport.GSDMB | X-ray crystallography | disease risk polymorphism | complex trait inflammatory disease | lipid binding

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“…Members of the protein family that share motifs with DFNA5 that are described in the literature are cancerassociated (Saeki et al, 2000;Thompson and Weigel, 1998;Lage et al, 2001;Watabe et al, 2001) (see http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF04598 for DFNA5 family). This is particularly compelling because high levels of HA are a prognostic indicator for malignancy in clinical cases of human breast, ovarian and colon carcinomas.…”

Section: The Role Of Ha In the Developing Earmentioning

confidence: 99%

The deafness genedfna5is crucial forugdhexpression and HA production in the developing ear in zebrafish

et al. 2004

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Over 30 genes responsible for human hereditary hearing loss have been identified during the last 10 years. The proteins encoded by these genes play roles in a diverse set of cellular functions ranging from transcriptional regulation to K+ recycling. In a few cases, the genes are novel and do not give much insight into the cellular or molecular cause for the hearing loss. Among these poorly understood deafness genes is DFNA5. How the truncation of the encoded protein DFNA5 leads to an autosomal dominant form of hearing loss is not clear. In order to understand the biological role of Dfna5, we took a reversegenetic approach in zebrafish. Here we show that morpholino antisense nucleotide knock-down of dfna5 function in zebrafish leads to disorganization of the developing semicircular canals and reduction of pharyngeal cartilage. This phenotype closely resembles previously isolated zebrafish craniofacial mutants including the mutant jekyll. jekyll encodes Ugdh [uridine 5′-diphosphate (UDP)-glucose dehydrogenase], an enzyme that is crucial for production of the extracellular matrix component hyaluronic acid (HA). In dfna5 morphants, expression of ugdh is absent in the developing ear and pharyngeal arches, and HA levels are strongly reduced in the outgrowing protrusions of the developing semicircular canals. Previous studies suggest that HA is essential for differentiating cartilage and directed outgrowth of the epithelial protrusions in the developing ear. We hypothesize that the reduction of HA production leads to uncoordinated outgrowth of the canal columns and impaired facial cartilage differentiation.

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Structure, Expression and Chromosome Mapping of MLZE, a Novel Gene Which Is Preferentially Expressed in Metastatic Melanoma Cells

Cited by 91 publications

References 25 publications

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein

The deafness genedfna5is crucial forugdhexpression and HA production in the developing ear in zebrafish

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