Molecular disruption of oncogenic signal transducer and activator of transcription 3 (STAT3) protein.
Signal transducer and activator of transcription protein 3 (STAT3) is a latent cytosolic transcription factor that is widely recognized as being a master regulator of the cellular functions that lead to the cancer phenotype. Constitutively activated STAT3 protein activity is routinely observed in human cancers, promoting uncontrolled cell proliferation and suppressing apoptosis. Until relatively recently, inhibition of STAT3 transcriptional activity was achieved indirectly via suppression of upstream kinase activators and extracellular cytokine and (or) growth factor stimuli. However, activated STAT3 forms transcriptionally functional STAT3-STAT3 dimers, providing a valid juncture for targeted downstream molecular inhibition. STAT3's prominent role in cancer has seen a decade of innovative and novel approaches to targeting constitutively active STAT3 protein-protein complexes. This mini-review outlines the progress made towards identifying molecular agents capable of silencing aberrant STAT3 signalling through the disruption of STAT3 complexation events.
Fletcher
Steven
S
Department of Chemistry, 3359 Mississauga Road North, South Building, Rm 4046, University of Toronto, Mississauga, ON L5L 1C6.
Drewry
Joel A
JA
Shahani
Vijay M
VM
Page
Brent D G
BD
Gunning
Patrick T
PT
D050822:Cytokine Receptor gp130 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation
D019151:Peptide Library; D010455:Peptides; D050796:STAT3 Transcription Factor; D050822:Cytokine Receptor gp130