A new protagonist in cell survival
What do solid tumours, certain congenital types of deafness and rheumatoid arthritis have in common? A deregulation in the function of the protein KIAA1199! In a study published in Nature communications, researchers from the University of Liège reveal the link between this protein and a receptor known as EGFR, a key protagonist in tumour development and progression. A link that could be of importance for these human diseases...
A protein that activates some key survival pathways
Within the framework of its research on familial cylindromatosis, Alain Chariot’s team studied the cellular consequences of overexpressing Bcl-3. What happens in cells when this protein is expressed in large amounts? "We used the DNA chip approach to identify all gene candidates induced following the overexpression of Bcl-3 in immortalized keratinocytes. The most intensively induced candidate upon Bcl-3 overexpression was KIAA1199". Following these observations, the researchers made the link with another disease in which keratinocytes are proliferating too much: cervical cancer. “This cancer results from an infection by the oncogenic human papillomavirus (HPV). When patients develop this type of cancer following HPV infection, they also exhibit large amounts of the Bcl-3 protein, which leads to the overexpression of its target gene KIAA1199", explains Alain Chariot, who established a fruitful collaboration with the team of Professor Philippe Delvenne at GIGA’s Laboratory of Experimental Pathology, ULg. But why does HPV induce this gene? It was still unclear at that time what the KIAA1199 protein was actually doing. The researchers from Liège provided some answers to this question in an article published in Nature Communications (1). “We show that this protein promotes cell survival in keratinocytes. If we deprive these cells from the protein KIAA1199, the keratinocytes die. The overexpression of this gene is therefore one of the reasons why patients develop cervical cancer, because HPV triggers the expression of this protein to sustain cell survival in the infected keratinocytes. As they survive longer, cancerous cells can accumulate and tumor growth occurs", Alain Chariot reveals.
(1) Kateryna Shostak, Xin Zhang, Pascale Hubert, Serkan Ismail Göktuna, Zheshen Jiang, Iva Klevernic, Julien Hildebrand, Patrick Roncarati, Benoit Hennuy, Aurélie Ladang, Joan Somja, André Gothot, Pierre Close, Philippe Delvenne & Alain Chariot. NF-κB-induced KIAA1199 promotes survival through EGFR signalling. Nature communications| 5:5232 | DOI: 10.1038/ncomms6232 |