The Wnt signaling pathway controls cell-cell communication by transmitting signals from cell surface receptors to DNA expression in the nucleus. It regulates beta-catenin, which enters the nucleus to activate gene expression. Mutations that damage the pathway prevent proper control of beta-catenin, leading to over-expression of genes involved in diseases like cancer. Drugs targeting components of the Wnt pathway like beta-catenin show promise for treating cancers caused by alterations in this important signaling network.

1. Under supervision of :
DR/AHMAD EL MALKY

2. The Wnt signaling pathway is a network of proteins
that passes signals from receptors on the surface of
the cell to DNA expression in the nucleus. It
controls cell-cell communication in the embryo and
adult .
The Wnt signaling pathway controls beta-catenin,
which enters the nucleus, binds to DNA, and turns
on the expression of genes. By its control of the
phosphatase PPA2, Wnt signaling inhibits
phosphorylation of beta-catenin, thereby inhibiting
the degradation of beta-catenin. When the pathway
is damaged by mutations, it can no longer control
beta-catenin, and those genes are over-expressed.
The pathway is therefore a target for drugs to
control these diseases

4. Members
The following is a list of human genes that encode
WNT signaling proteins:
WNT1
WNT2, WNT2B
WNT3, WNT3A
WNT4
WNT5A, WNT5B
WNT6
WNT7A, WNT7B
WNT8A, WNT8B
WNT9A, WNT9B
WNT10A
WNT10B, WNT11
WNT16

5. Figure 1. Wnt doesn't bind
to the receptor. Axin, GSK
and APC form a "destruction
complex," and β-Cat is
destroyed.

6. Figure 2. Wnt binds to (activates)
the receptor. Axin is removed
from the "destruction complex."
β-Cat moves into the nucleus,
binds to a transcription factor on
DNA, and activates transcription
of a protein. "P" represents
phosphate.

7. Wnt-induced cell responses:
Several important effects of the canonical Wnt
pathway include:
Cancers. Alterations of Wnts, APC, axin, and
TCFs are all associated with carcinogenesis.
Induction of Insulin receptor substrate 1 (IRS-
1). IRS-1 induction activates mitochondrial
biogenesis leading to increased oxidative
damage, depletion of stem cells, and
predisposition to some types of cancer.

8. In the normal pathway, APC and Axin prevent
β-catenin from traveling to the nucleus by
engaging it in the destruction complex.
However, an APC deficiency or mutations to
β-catenin that prevent its degradation can
lead to excessive stem cell renewal and
proliferation, predisposing the cells to the
formation of tumors.
Alteration of Wnt5a, a tumor suppressor
gene, could also lead to tumor formation.

9. One of the potential ways to treat cancer is to
affect β-catenin, a central component of the
canonical Wnt pathway. Non-steroidal anti-
inflammatory drugs (NSAIDs) that interfere β-
catenin signaling have been shown to be
promising for the prevention of colorectal cancer.
NSAIDs inhibit prostaglandin production, which
interferes with β-catenin/TCF-dependent
transcription.
Another suggested method of treatment is to use
natural antagonists of the Wnt pathway, such as
secreted frizzled-related proteins (sFRPs) or Dkk.
Furthermore, using small molecules to block the
interaction between β-catenin and TCF could
stop the proliferation of cancer.

10. Researchers have also developed a
recombinant adenovirus (Ad-CBR) that
constitutively expresses the β-catenin
binding domain of APC.[46] This enables the
tumor suppressor activity of APC, thus
preventing β-catenin translocation to the
nucleus. Scientists are also using monoclonal
antibodies against Wnt proteins to induce
apoptosis in cancer cells