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. Author manuscript; available in PMC: 2010 Dec 1.
Published in final edited form as: Pigment Cell Melanoma Res. 2009 Aug 25;22(6):724–739. doi: 10.1111/j.1755-148X.2009.00627.x

Table 1.

Ligand Function Reference
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

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

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
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

Katoh et al., 1996; Rhee et al., 2002; Benhal et al., 2006; Khan et al., 2007
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

Roelink et al., 1993; Chen et al., 2008; Chein et al., 2009
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

Ungar, Kelly, and Moon, 1995; Carroll, Wallingford, and Vize, 1999; Jeays-Ward et al., 2003; Miyakoshi et al., 2008; Boyer et al., 2009
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

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
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

Saitoh and Katoh, 2001; Morioka et al., 2009; Mangioni et al., 2005; Saitoh and Katoh, 2002
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

Wolda and Moon, 1992; Rankin et al., 1999; Schmidt et al., 2007; Lavery et al., 2008
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

Riddle et al., 1995; Le Grand et al., 2009; Heasley and Winn, 2008
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

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

Swiatek et al., 2004
WNT8B
  • Located on chromosome 10q24

  • WNT8B plays a key role in regulating proliferation of lens stem/progenitor cells and during early stages of fiber cell differentiation

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

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

Juriloff et al., 2006; Jezewski et al., 2008
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

Nawaz et al., 2009; Ordway et al., 2006
WNT10B (WNT12)
  • Located chromosome: 12q13

  • Highly expressed in nevi and also in melanomas characterized by small, uniform cells and by large, pleomorphic cells

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

Katoh, 2005; Ulrich et al., 2005; Wai et al., 2002
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

Mazieres et al., 2005; Casagrande et al., 2006