CJC is published 12 times a year.
Sign up for Table of Contents Alerts!
Please note: CJC is published in English and Chinese. Manuscripts are published online prior to printing. The citation will change as volume, issue and page numbers are finalized.
Email this page
Print this page
Mini-review
Fiber, Cancer Stem Cells, and the Wnt Signaling Continuum:
Possibilities for Colorectal Cancer Prevention and Therapeutics
Michael Bordonaro and Alan C. Sartorelli
volume 27 | issue 7
July 2008Subscribe to this journal for $0/year
Wnt signaling is implicated in the initiation of human colorectal cancer (CRC). While the relationship between Wnt activity and proliferation is well known, studies have also shown an association between high levels of Wnt activity and apoptosis. Through analyses of ten human CRC cell lines, we have found that inhibitors of histone deacetylases (HDACis), such as butyrate, promote apoptosis of CRC cells through hyper-induction of Wnt signaling; thus, hyper-activation of Wnt activity by HDACis may represent a novel preventive and therapeutic strategy against CRC. Our findings may explain why studies on the protective role of dietary fiber and its product butyrate against CRC have yielded inconsistent findings. We believe that the variability in the levels of induced Wnt activity and apoptosis in CRC cells observed in vitro reflects the in vivo existence of CRC subtypes with variable degrees of responsiveness to butyrate. Given that Wnt activity has been linked to intestinal stem cell renewal and the migratory potential of CRC stem cells, this essay will discuss the potential of modulation of Wnt signaling by HDACis as a therapeutic approach against CRC stem cells. Finally, we consider possible gene therapy approaches that target Wnt-positive CRC stem cells.
Authors
Michael Bordonaro
Yale University School of Medicine
Alan C. Sartorelli
Yale University School of Medicine