Targeting a protein in order to fight against intestinal cancer
As recently stated by The Foundation Against Cancer, “cancer of the large intestine is the second most common form of cancer in both males and females in Belgium and it is also the second most common cause of death by cancer in our country”. More than 8,500 new cases were diagnosed in 2012. In a recent study (1), Alain Chariot and Pierre Close, of GIGA (University of Liege) identified the gene coding for the ELP3 protein as a key factor in the development of intestinal tumours.
Double role of Wnt
To ensure that this intestinal regeneration and therefore the proliferation of stem cells and the differentiation of cells emerging from the transit-amplifying compartment occurs, there is a mechanism called the Wnt signalling pathway. When this is not activated, there is no proliferation. It must be activated in a transitory manner at the right time. When the Wnt signalling pathway is not active, a complex of proteins – axin, glycogen synthase kinase 3β (GSK3β) and APC (adenomatous polyposis coli) – degrade the β-catenin, another protein which plays a role in cellular signalling. The objective is to make sure that β-catenin is expressed in small quantities. If β-catenin is no longer degraded, it accumulates in the cytoplasm then moves into the nucleus of the cell, associates with LEF-1 /TCF transcription factors to induce the expression of several genes which will ultimately leads to cell proliferation. The transient stabilization of β-catenin takes place when ligands bind to a specific receptor and trigger the Wnt signalling pathway which ultimately prevents the complex of proteins required for the degradation of β-catenin from fulfilling its role.
(1) Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine. A. Ladang*, F. Rapino*, L.C. Heukamp, L. Tharun, K. Shostak, D. Hermand, S. Delaunay, I. Klevernic, Z. Jiang, N. Jacques, D. Jamart, V. Migeot, A. Florin, S. Göktuna, B. Malgrange, O.J. Sansom, L. Nguyen, R. Büttner, P. Close*, A. Chariot*.