Wnt Pathway in Cancer Stem Cells
The canonical and non-canonical pathways show that the Wnt pathway is strictly regulated by many different elements. Thus, it can be expected that misregulation of these various components can have drastic effects throughout an organism. One interesting aspect of the Wnt pathway in particular is its involvement in the fate of stem cells and its role as a regulator of stem cell choice to proliferate or self-renew. Given these properties, it is not surprising that a strong correlation between Wnt signaling and the onset of cancer exists. 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.
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. Researchers have also developed a recombinant adenovirus (Ad-CBR) that constitutively expresses the β-catenin binding domain of APC. 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. Currently, there are many investigations underway to target various components of the Wnt pathway as a means of finding more effective treatments for cancer.
Read more about this topic: Wnt Signaling Pathway
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