Abstract
In recent years, several antitumor signaling pathways mediated by the cGMP-dependent protein kinases have been identified in colon cancer cells. This review aims to present the mounting evidence in favor of cGMP/protein kinase G (PKG) signaling as a therapeutic strategy in colon cancer. The homeostatic and tumor suppressive effects of cGMP in the intestine are uncontested, but the signaling details are not understood. PKG is the central cGMP effector, and can block proliferation and tumor angiogenesis by inhibiting β-catenin/TCF and SOX9 signaling. Therapeutic activation of cGMP/PKG offers a promising avenue for the prevention and treatment of colon cancer, but additional preclinical studies are needed to fully understand the potential of this system.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Anticarcinogenic Agents / pharmacology*
-
Anticarcinogenic Agents / therapeutic use*
-
Cell Line, Tumor
-
Colonic Neoplasms / drug therapy*
-
Colonic Neoplasms / metabolism*
-
Colonic Neoplasms / pathology
-
Colonic Neoplasms / prevention & control*
-
Cyclic GMP-Dependent Protein Kinases / chemistry
-
Cyclic GMP-Dependent Protein Kinases / genetics
-
Cyclic GMP-Dependent Protein Kinases / metabolism*
-
Enzyme Activation
-
Homeostasis
-
Humans
-
Intestinal Mucosa / metabolism
-
Intestines / pathology
-
Protein Conformation
-
SOX9 Transcription Factor / metabolism
-
Signal Transduction / drug effects*
-
Signal Transduction / physiology
-
beta Catenin / metabolism
Substances
-
Anticarcinogenic Agents
-
SOX9 Transcription Factor
-
SOX9 protein, human
-
beta Catenin
-
Cyclic GMP-Dependent Protein Kinases