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Wnt is an anti-apoptotic ligand for the Fz (frizzled) receptor on cell membranes
Wnt is an anti-apoptotic ligand for the Fz (frizzled) receptor on cell membranes, meaning it attaches to the Fz receptor and prevents cell death (in effect with other cellular stimuli). Wnt molecules are a family of proteins that act as a paracrine stimulus for cells, since it is secreted by others into the intra-cellular matrix surrounding all cells. Downstream of Wnt attachment to Fz, B-cat molecules remain intact and the cell is permitted to enter the cell cycle and replicate.
The consequences of cell cycle are many – in cancer, this allows the tumour to grow whilst in other tissues it permits healthy growth and repair.
Because of its extra-cellular location of action, Wnt is an effective signalling molecule between cells, and can influence large areas of tissue dispersing through the extra-cellular matrix.
The significance of Wnt in tumour genesis has been realised, but has yet to be translated into therapeutic potential directly. Because of the downstream effects of Wnt are far more specific than the action of Wnt at the cell membrane, targeting Wnt can often produce a number of unwanted side effects because of its global influence on cellular homeostasis. For example, Wnt is implicated in upper limb development and associated abnormalities. It is very important molecule in development, implicated in the development of the heart in addition to limbs, through downstream cascades and signalling pathways such as catenin. In mouse, they have a role in lung development, which is likely to be replicated in many other species too.
Although difficult to translate to therapeutics directly, this knowledge opens many doors for further research in the field which will shine light on developmental abnormalities and their possible causes.
However, Wnt is a key regulator of many significant molecules such as B-cat, Hedgehog, MTM and catenin in the apoptotic pathway and therefore, remains of significant interest to those researching oncology.
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