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Published on: January 12, 2020
Mutated in colorectal cancer protein modulates the NFκB pathway
Nicholas D Sigglekow1, Laurent Pangon, Tilman Brummer
1Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Sydney NSW 2010, Australia.
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.
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