Anti-Inflammation and Colon Rectal Cancer

Dr. Weeks’ Comment:   Here is another example of how beneficial anti-inflammatory agents are in cancer since anti-inflammatory agents inhibit NIK.

NIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach.

TNIK inhibition abrogates colorectal cancer stemness

  • Mari Masuda  et al 
  • NATURE  Nature Communications Article number: 12586 doi:10.1038/ncomms12586 Published 26 August 2016
  • http://www.nature.com/ncomms/2016/160826/ncomms12586/full/ncomms12586.html

ABSTRACT  Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik−/−/Apcmin/+mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach.

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Dr. Weeks’ Comment:   Here is another example of how beneficial anti-inflammatory agents are in cancer since anti-inflammatory agents inhibit NIK. NIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. TNIK inhibition abrogates colorectal cancer stemness Mari Masuda  et al  NATURE  Nature Communications Article number:…
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