Under supervision of :

DR/AHMAD EL MALKY

proteinsis a network of signaling pathwayWntThe 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 .

, catenin-betasignaling pathway controls WntThe which enters the nucleus, binds to DNA, and turns on the expression of genes. By its control of the

signaling inhibits Wnt, 2PPAphosphatasephosphorylation 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

Members

The following is a list of human genes that encode WNT signaling proteins:

WNT1

B2WNT, 2WNT

A3WNT, 3WNT

4WNT

B5WNT, A5WNT

6WNT

B7WNT, A7WNT

B8WNT, A8WNT

B9WNT, A9WNT

A10WNT

11WNT, B10WNT

16WNT

Figure 1. Wnt doesn't bind to the receptor. Axin, GSK

and APC form a "destruction complex," and β-Cat is

destroyed.

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

Wnt-induced cell responses:

Several important effects of the canonical Wntpathway include:

Cancers. Alterations of Wnts, APC, axin, and TCFs are all associated with carcinogenesis.

-(IRS1Insulin receptor substrate Induction of mitochondrial induction activates 1 -). IRS1

oxidative leading to increased biogenesis, and stem cells, depletion of damage

predisposition to some types of cancer.

prevent Axinand APCIn the normal pathway, from traveling to the nucleus by catenin-β

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.

tumor suppressor a, a 5Alteration of Wnt., could also lead to tumor formationgene

One of the potential ways to treat cancer is to affect β-catenin, a central component of the canonical Wnt pathway. Non-steroidal anti-

-) that interfere βNSAIDsinflammatory drugs (catenin signaling have been shown to be

. colorectal cancerpromising for the prevention of production, which prostaglandinNSAIDs inhibit

interferes with β-catenin/TCF-dependent transcription.

Another suggested method of treatment is to use pathway, such as Wntof the antagonistsnatural

. Dkk) or sFRPsrelated proteins (-secreted frizzledto block the small moleculesFurthermore, using

interaction between β-catenin and TCF could stop the proliferation of cancer.

Researchers have also developed a recombinant adenovirus (Ad-CBR) that constitutively expresses the β-catenin

This enables the ]46[binding domain of APC.tumor suppressor activity of APC, thus preventing β-catenin translocation to the

monoclonal nucleus. Scientists are also using proteins to induce Wntagainst antibodies

in cancer cellsapoptosis