title: cGMP-dependent protein kinases as potential targets for colon cancer prevention and treatment.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, CB2516, Augusta, GA 30912, USA. dbrowning@mcg.edu
authors.forename: Darren D
authors.initials: DD
authors.lastname: Browning
authors.forename: In-Kiu
authors.initials: IK
authors.lastname: Kwon
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D011487:Protein Conformation; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D051176:beta Catenin; D017869:Cyclic GMP-Dependent Protein Kinases