Mutated in colorectal cancer protein modulates the NFκB pathway.

The tumour suppressor gene 'mutated in colorectal cancer' (MCC) is silenced through promoter methylation in colorectal cancer and has been implicated as a regulator of the nuclear factor kappa B (NFκB) pathway. Therefore, we aimed to determine whether MCC modulates NFκB activation in colorectal cancer. NFκB activation was assessed using luciferase reporter assays in colorectal cancer cells in vitro. MCC methylation was analysed in primary tumour specimens from patients with inflammatory bowel disease. Re-expression of MCC reduced NFκB-dependent transcription in tumour necrosis factor alpha (TNFα)- or lipopolysaccharide (LPS)-stimulated cells. Conversely, knockdown of MCC resulted in accumulation of the inhibitor of kappa B alpha (IκBα) protein, encoded by NFKBIA, a first response gene specifically and rapidly regulated by NFκB pathway activation. The MCC gene is methylated in up to 6/16 of inflammatory bowel disease-associated tissue specimens, and myosin-10 and valosin-containing protein were identified as MCC-interacting proteins. These findings suggest that MCC modulates NFκB pathway signalling indirectly in colorectal cancer cells.

Citation

Nicholas D Sigglekow, Laurent Pangon, Tilman Brummer, Mark Molloy, Nicholas J Hawkins, Robyn L Ward, Elizabeth A Musgrove, Maija R J Kohonen-Corish. Mutated in colorectal cancer protein modulates the NFκB pathway. Anticancer research. 2012 Jan;32(1):73-9

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PMID: 22213290

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