The paracrine hormone hypothesis of colorectal cancer.

Authors

• G M Pitari
• P Li
• J E Lin
• D Zuzga
• A V Gibbons
• A E Snook
• S Schulz
• S A Waldman

Publication/Presentation Date

10-1-2007

Abstract

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.

Volume

82

Issue

4

First Page

441

Last Page

447

ISSN

0009-9236

Published In/Presented At

Pitari, G. M., Li, P., Lin, J. E., Zuzga, D., Gibbons, A. V., Snook, A. E., Schulz, S., & Waldman, S. A. (2007). The paracrine hormone hypothesis of colorectal cancer. Clinical pharmacology and therapeutics, 82(4), 441–447. https://doi.org/10.1038/sj.clpt.6100325

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

17687268

Department(s)

Administration and Leadership

Document Type

Article