• COLORECTAL CARCINOMA
• STEM CELLS
• POLYPOSIS
• ONCOGENES
• MOLECULAR CARCINOGENESIS

If there is one cancer signalling pathway that Gut readers should be comfortable with, it is the Wnt pathway. Central to this pathway is the adenomatous polyposis coli (APC) gene responsible for familial adenomatous polyposis. Identification of the APC gene in 1991 heralded the start of an ongoing period of exponential growth in our understanding of the molecular basis of cancer, particularly of the large bowel. Clinicians can perhaps be forgiven for finding the ever-expanding list of genes and interacting pathways with their inaccessible names and acronyms daunting. For many, the paper in this issue by Elvira Bakker and coworkers at the Netherlands Cancer Institute revealing the detailed role of RSPO3 in colorectal carcinogenesis may only serve to widen the expanding clinician–researcher divide. However, those brave enough to dive deeper into this paper will be rewarded with an insight into the current state of the art of molecular research into colorectal cancer with an intriguing mix of confirmation of what we thought we knew and findings that challenge previous assumptions.

R-spondin 3 (RSPO3) is a secreted protein that acts to potentiate Wnt signalling. RSPOs first attracted attention as being specific ligands of the LGR5 (leucine-rich repeat-containing G-protein-coupled receptor …