Colorectal cancer tumorigenesis (from Cancer Prevention Research)

Certain driver mutations give intestinal stem cells a major proliferative advantage, but healthy stem cells can still potentially prevail and prevent onset of colorectal cancer (CRC). Three studies now reveal ‘supercompetitor’ strategies that mutated stem cells use to sabotage their neighbors and stack the odds of tumorigenesis. Roughly 80% of CRC tumors exhibit mutations inactivating the tumor-suppressor Apc, and van Neerven et al. used a co-culture system to study how organoids generated from Apc-negative cells influence wild-type organoids. They determined that mutant organoids secrete molecular signals including a protein called NOTUM that force wild-type intestinal stem cells to stop proliferating and differentiate by switching off WNT signaling, which is permanently activated in Apc-mutant cells. Flanagan et al. also homed in on this same protein, and conducted mouse model studies demonstrating that NOTUM inhibits wild-type stem cell proliferation in...

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