c-Src Constitutes a Bridge between the CFTR Failure and MUC1 Overexpression in Cystic Fibrosis

What is it about?

Cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) chloride channel, is associated in the respiratory system with the accumulation of mucus and impaired lung function. The role of the CFTR channel in the regulation of the intracellular pathways that determine the overexpression of mucin genes is unknown. Using differential display, we have observed the differential expression of several mRNAs that may correspond to putative CFTR-dependent genes. One of these mRNAs was further characterized, and it corresponds to the tyrosine kinase c-Src. Additional results suggest that c-Src is a central element in the pathway connecting the CFTR channel with MUC1 overexpression and that the overexpression of mucins is a primary response to CFTR malfunction in cystic fibrosis, which occurs even in the absence of bacterial infection.

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Why is it important?

This is the first indication that CFTR have a signaling pathway, in which c-Src constitutes one of the steps. Also shows that increased MUC1 expression in CF cells is due to an intrinsic failure in CF cells and not due to the subsequent infections. Related work from our lab: 1: Massip-Copiz MM, Clauzure M, Valdivieso ÁG, Santa-Coloma TA. CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling. Arch Biochem Biophys. 2017 Feb 15;616:1-12. doi: 10.1016/j.abb.2017.01.003. Epub 2017 Jan 11. PubMed PMID: 28088327. 2: Massip Copiz MM, Santa Coloma TA. c- Src and its role in cystic fibrosis. Eur J Cell Biol. 2016 Oct;95(10):401-413. doi: 10.1016/j.ejcb.2016.08.001. Epub 2016 Aug 11. Review. PubMed PMID: 27530912. 3: Valdivieso AG, Santa-Coloma TA. CFTR activity and mitochondrial function. Redox Biol. 2013 Feb 5;1:190-202. doi: 10.1016/j.redox.2012.11.007. Review. PubMed PMID: 24024153; PubMed Central PMCID: PMC3757715.

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