The Role of M3 Muscarinic Receptor Ligand-Induced Kinase Signaling in Colon Cancer Progression.
Publication/Presentation Date
3-5-2019
Abstract
Despite a reduction in incidence over the past decade, colon cancer remains the second most common cause of cancer death in the United States; recent demographics suggest this disease is now afflicting younger persons. M₃ muscarinic receptor (M₃R) mRNA and protein are over-expressed in colon cancer, and M₃R can be activated by both traditional (e.g., acetylcholine) and non-traditional (e.g., bile acids) muscarinic ligands. In this review, we weigh the data supporting a prominent role for key protein kinases downstream of M₃R activation in promoting colon cancer progression and dissemination. Specifically, we explore the roles that downstream activation of the mitogen activated protein kinase/extracellular signal-related kinase (MAPK/ERK), protein kinase C, p38 MAPK, and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathways play in mediating colon cancer cell proliferation, survival, migration and invasion. We assess the impact of M₃R-stimulated induction of selected matrix metalloproteinases germane to these hallmarks of colon cancer progression. In this context, we also critically review the reproducibility of findings derived from a variety of in vivo and in vitro colon cancer models, and their fidelity to human disease. Finally, we summarize the therapeutic potential of targeting various steps from ligand-M₃R interaction to the activation of key downstream molecules.
Volume
11
Issue
3
ISSN
2072-6694
Published In/Presented At
Tolaymat, M., Larabee, S. M., Hu, S., Xie, G., & Raufman, J. P. (2019). The Role of M3 Muscarinic Receptor Ligand-Induced Kinase Signaling in Colon Cancer Progression. Cancers, 11(3), 308. https://doi.org/10.3390/cancers11030308
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
30841571
Department(s)
Department of Pediatrics
Document Type
Article