WNT1 |
Located on chromosome 12q13
Proto-oncogene
Involved in chromosomal rearrangements in a wide range of cancers
Involved in cell proliferation, motility, patterning, embryonic development, fate determination, and carcinogenesis
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Rijsewijk et al., 1987; Arheden et al., 1988 |
WNT2A (WNT13) |
Located on chromosome 7q31.2
WNT2 was shown to have a similar protein sequence, biochemical properties, and transforming potential as WNT1
Involved in angiogenesis, overexpressed in colorectal cancer, and upregulated in melanoma
One study suggests that use of a monoclonal antibody against WNT2 may be useful as a treatment for malignant melanoma as it was shown to induce apoptosis in human melanoma cells overexpressing WNT2
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Wainwright et al., 1988; Blasband et al., 1992; Klein et al., 2009; Park et al., 2009; Kashani-Sabet et al., 2009; You et al., 2004
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WNT2B |
Located on chromosome 1p13
372 amino acids, including a signal peptide, two potential N-glycosylation sites, and 24 cysteine residues
Detected in the heart, placenta, brain, prostate, lung, testis, ovary, small intestine, and colon of adult human, as well as the lung, kidney, and brain of fetal human
Role in cancer, including head and neck squamous cell carcinomas, breast cancer, and acute lymphoblastic leukemia
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Katoh et al., 1996; Rhee et al., 2002; Benhal et al., 2006; Khan et al., 2007
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WNT3A |
Located on chromosome 1q42
Induces Dvl phosphorylation, β-catenin stabilization, and TCF4 transcriptional activity
WNT3A expressing B16 mouse melanoma cells exhibit decreased tumor size and decreased metastasis when implanted into mice
Upregulates genes implicated in melanocyte differentiation, several of which are downregulated with melanoma progression
May alter melanoma cell fate to a less proliferative and less aggressive phenotype
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Roelink et al., 1993; Chen et al., 2008; Chein et al., 2009
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WNT4 |
Located on chromosome 1p36.23-p35.1
Major role in development which affects morphogenesis in the zebrafish embro when misexpressed, including: misfolding in the brain, cyclopia, and an anteriorly forking notochord
Important in kidney pattern formation in Xenopus and cell migration in the developing mammalian gonad
In pituitary adenoma cells, WNT4 is involved in proliferation and survival, acting through a β-catenin independent pathway
Acts as an early granulosa cell tumor marker in the testis
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Ungar, Kelly, and Moon, 1995; Carroll, Wallingford, and Vize, 1999; Jeays-Ward et al., 2003; Miyakoshi et al., 2008; Boyer et al., 2009
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WNT5A |
Located on chromosome 3p21-p14
Major role in melanoma proliferation and invasion
Microarray studies and SAGE analysis demonstrated the upregulation of WNT5A in metastatic cells, as well as the importance of intracellular calcium expression
Melanoma cells overexpressing WNT5A, through transfection with stably expressing constructs, have been shown to increase cell motility and invasive potential
Contributes to the epithelial to mesenchymal transition through activation of the non-canonical pathway and the inhibition of metastatic suppressors
Regulates the expression of tumor antigens via the expression of STAT3
Effects motility and invasion through filamin A cleavage via calpains
In addition to melanoma, WNT5A has been shown to be important in pancreatic cancer, breast cancer, and ovarian cancer
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Bittner et al., 2000; Weeraratna et al., 2004; Weeraratna et al., 2002; Dissanayake et al., 2007; Dissanayake et al., 2008; O’Connell et al., 2009; Schwartz et al., 2009; Ford et al., 2009; Badiglian Filho et al., 2009
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WNT5B |
Consists of 4 exons and is located on human chromosome 12p13.3
Moderately expressed in adult prostate and fetal brain, and weakly expressed in fetal lung, kidney, adult liver, small intestine, and ovary
Important in osteosarcomas and is overexpressed in leiomyoma, esophageal, and breast cancer cells
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Saitoh and Katoh, 2001; Morioka et al., 2009; Mangioni et al., 2005; Saitoh and Katoh, 2002
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WNT6 |
First isolated in xenopus and mapped to human chromosome band 2q35 by in situ hybridization
Important during heart muscle generation and amniote neural crest induction through the non-canonical signaling pathway
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Wolda and Moon, 1992; Rankin et al., 1999; Schmidt et al., 2007; Lavery et al., 2008
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WNT7A |
Located on chromosome 3p25
Important in dorsoventral patterning in the limb
Recently shown to activate the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells, subsequently regulating the regenerative potential of muscle
Activates the JNK pathway in non-small cell lung cancer cells
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Riddle et al., 1995; Le Grand et al., 2009; Heasley and Winn, 2008
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WNT7B |
Located on chromosome 22q13
Stimulates embryonic lung growth by increasing the replication of epithelium and mesenchyme
In melanoma, WNT7B is present, but at variable levels, whereas in nevi, WNT7B has been shown to be strongly expressed
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Rajagopal et al., 2008; Pham et al., 2003 |
WNT8A |
Located on chromosome 5q31
Activates casein kinase Iε (CKIε), a positive regulator of the canonical Wnt pathway
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Swiatek et al., 2004 |
WNT8B |
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Martinez et al., 2009 |
WNT9A (14) |
Located on chromosome 1q42
Involved in canonical signaling, mediated by FZD7/9
WNT9A is required for the proper morphogenesis of chick hepatocellular cords and the proliferation of hepatoblasts/hepatocytes
Involved in glycogen accumulation in hepatocytes
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Matsumoto et al., 2008 |
WNT9B (15) |
Located on chromosome 17q21
Mutated in multifactorial non-syndromic cleft lip
Distinct roles in directing morphogenetic movements of developing branchial arch elements
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Juriloff et al., 2006; Jezewski et al., 2008
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WNT10A |
Located on chromosome 2q35
Mutation associated with a complete Odonto-Onycho- Dermal Dysplasia syndrome
Target of epigenetic inactivation in primary glial tumors and tumor cell lines
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Nawaz et al., 2009; Ordway et al., 2006
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WNT10B (WNT12) |
Located chromosome: 12q13
Highly expressed in nevi and also in melanomas characterized by small, uniform cells and by large, pleomorphic cells
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Pham et al., 2003 |
WNT11 |
Located on chromosome 11q13.5
A non-canonical WNT ligand
Functions in gastrulation by controlling cell cohesion
Highly expressed in neuroblastomas
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Katoh, 2005; Ulrich et al., 2005; Wai et al., 2002
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WNT16 |
Located on chromosome 7q31
Involved in human acute lymphoblastoid leukemia
Aberrant expression of WNT16 may be a key step in leukemogenesis in t(1;19)-positive pre-B leukemia cells
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Mazieres et al., 2005; Casagrande et al., 2006
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