Mutated in colorectal cancer protein modulates the NFκB pathway

Nicholas D. Sigglekow, Laurent Pangon, Tilman Brummer, Mark Molloy, Nicholas J. Hawkins, Robyn L. Ward, Elizabeth A. Musgrove, Maija R J Kohonen-Corish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: These findings suggest that MCC modulates NFκB pathway signalling indirectly in colorectal cancer cells.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalAnticancer Research
Volume32
Issue number1
Publication statusPublished - Jan 2012

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