Mutated in colorectal cancer protein modulates the NFκB pathway

Sigglekow, Nicholas D., Pangon, Laurent, Brummer, Tilman, Molloy, Mark, Hawkins, Nicholas J., Ward, Robyn L., Musgrove, Elizabeth A. and Kohonen-Corish, Maija R. J. (2012) Mutated in colorectal cancer protein modulates the NFκB pathway. Anticancer Research, 32 1: 73-79.

Author Sigglekow, Nicholas D.
Pangon, Laurent
Brummer, Tilman
Molloy, Mark
Hawkins, Nicholas J.
Ward, Robyn L.
Musgrove, Elizabeth A.
Kohonen-Corish, Maija R. J.
Title Mutated in colorectal cancer protein modulates the NFκB pathway
Journal name Anticancer Research   Check publisher's open access policy
ISSN 0250-7005
Publication date 2012-01
Sub-type Article (original research)
Open Access Status Not yet assessed
Volume 32
Issue 1
Start page 73
End page 79
Total pages 7
Place of publication Attiki, Greece
Publisher International Institute of Anticancer Research
Language eng
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.
Keyword Colorectal cancer
Inflammatory bowel disease
NF kappa B pathway
Valosin-containing protein
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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