Send to

Choose Destination
Clin Pharmacol Ther. 2007 Oct;82(4):441-7. Epub 2007 Aug 8.

The paracrine hormone hypothesis of colorectal cancer.

Author information

Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.


Colorectal carcinogenesis originates in the context of dysregulated epithelial cell homeostasis, wherein hyperproliferation, hypodifferentiation, metabolic reprogramming, and mesenchymal remodeling reflect recursive mutually reinforcing mechanisms contributing to progressive genomic instability. Although genotypic and phenotypic elements characterizing the terminal integration of these pathophysiological processes defining cancer are well enumerated, events initiating, coordinating, and sustaining this hierarchical maladaptive systems evolution remain elusive for most tumors. In the intestine, guanylyl cyclase C (GCC) and its paracrine ligands organize and regulate the homeostatic integrity of the crypt-villus axis, forming a hormonal tumor suppressor signaling sequence, whose dysfunction defines the initiation of neoplastic transformation and creates a permissive niche for tumor progression.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center