Biomedical Engineering Reference
In-Depth Information
Table 1 Examples of Wnt transduction in human cancers
Tumor
Authors
Notes
Adenocarcinoma
of the colon
Suzuki et al. (2004)
Restoration of SFRP in colorectal cancer cells
limits WNT signaling
Adenocarcinoma
of the lung
You et al. (2004)
Inhibition of Wnt2-mediated signaling
induces apoptosis through inactivation of
Survivin
Lymphoblastic
leukemia
Chung et al. (2002)
Overexpression of dominant negative beta-
catenin or dominant TCF inhibits
proliferation
Multiple
myeloma
Derksen et al. (2004)
Stimulation of growth by Wnt ligands.
Dominant negative TCF-4 inhibits growth
Oral squamous
cell carcinoma
Sogabe et al. (2008)
Ectopic expression of SFRPs inhibits cancer
cell proliferation in vitro
Osteosarcoma
Hoang et al.
(2004a,b)
Expression of Dkk-3 and LRP5 inhibits cancer
cell growth in vitro
Pleural
mesothelioma
Lee et al. (2004)
Restoration by transfection of the SFRP gene
construct into cell lines lacking SFRP
expression results in apoptosis and growth
suppression
(NSCLC) (Table 1). Indeed, Wnt2 is overexpressed in NSCLC and inhibition of
Wnt2-mediated signaling by siRNA or a monoclonal antibody leads to apop-
tosis in NSCLC cell lines (You et al., 2004). Wnt inhibitory factor (WIF1), a
secreted antagonist of Wnt, can inhibit growth both in vitro and in vivo in lung
adenocarcinoma cell lines (Kim et al., 2007). Hypermethylation of the WIF1
promoter is a common mechanism of anomalous silencing of WIF1 which leads
to activation of Wnt signaling in lung cancer (He et al., 2005). Abnormally high
expression of Disheveled 3 (Dvl-3), a positive regulator of Wnt, has been shown
to occur in about 75% of freshly microdissected NSCLC tumor specimens
(Uematsu et al., 2003).
2.1.2 The Non-canonical Wnt Pathway
In the Wnt/Ca2
þ
pathway, Wnt proteins signal through the activation of
calmodulin kinase II and protein kinase C, leading to an increase of intracel-
lular Ca2
þ
. Cell polarity can be influenced throughWnt via the Jun N-terminal
kinase (JNK) signaling cascade (Veeman et al., 2003). Wnt has also been
described to atypically signal via the receptor tyrosine kinase (RTK) pathway
(Oishi et al., 2003) and through a newly discovered cascade involving the cyclic
adenosine monophosphate (cAMP) pathway activating protein kinase A down-
stream of specific Wnts ultimately affecting myogenesis; the phosphorylation
and activation of the cAMP response element-binding (CREB) (Chen et al.,
2005) is a protagonist in this signaling pathway.
