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The Paracrine Hormone Hypothesis of Colorectal Cancer
Author(s) -
Pitari G M,
Li P,
Lin J E,
Zuzga D,
Gibbons A V,
Snook A E,
Schulz S,
Waldman S A
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100325
Subject(s) - paracrine signalling , biology , colorectal cancer , context (archaeology) , cancer research , carcinogenesis , aberrant crypt foci , neoplastic transformation , hormone , cancer , bioinformatics , endocrinology , genetics , receptor , paleontology , colonic disease
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. Clinical Pharmacology & Therapeutics (2007) 82 , 441–447; doi: 10.1038/sj.clpt.6100325 ; published online 8 August 2007