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dc.contributor.authorTolaymat, M.
dc.contributor.authorLarabee, S.M.
dc.contributor.authorHu, S.
dc.date.accessioned2019-09-13T17:02:31Z
dc.date.available2019-09-13T17:02:31Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85063375426&doi=10.3390%2fcancers11030308&partnerID=40&md5=d89d7c2cfd0dce193dfb51c93d5363cc
dc.identifier.urihttp://hdl.handle.net/10713/10796
dc.description.abstractDespite 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. M 3 muscarinic receptor (M 3 R) mRNA and protein are over-expressed in colon cancer, and M 3 R 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 M 3 R 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 M 3 R-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-M 3 R interaction to the activation of key downstream molecules. Copyright 2019 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorshipThis research was funded by the United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Program, VA Merit Award grant numbers BX002129 and BX002777. Mazen Tolaymat and Shannon M. Larabee were supported by the U.S. National Institutes of Health, grant number T32 DK067872.en_US
dc.description.urihttps://doi.org/10.3390/cancers11030308en_US
dc.language.isoen-USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancers
dc.subjectAcetylcholineen_US
dc.subjectBile acidsen_US
dc.subjectColon canceren_US
dc.subjectMuscarinic ligandsen_US
dc.subjectMuscarinic receptorsen_US
dc.titleThe role of M3 muscarinic receptor ligand-induced kinase signaling in colon cancer progressionen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers11030308


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