p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies.
Phosphorylation of the cyclin-dependent kinase inhibitor p27 by upstream mitogenic signaling pathways regulates its stability, localization, and biological function. In human cancers, loss of the antiproliferative action of p27 can arise through reduced protein levels and/or cytoplasmic mislocalization, leading to increased cell proliferation and/or cell migration, respectively. Reduced p27 expression levels and p27 mislocalization have potential prognostic and therapeutic implications in various types of human cancers. This review highlights mechanisms of functional deregulation of p27 by oncogenic signaling that provide an important molecular rationale for pathway targeting in cancer treatment.
Braman Family Breast Cancer Institute, University of Miami Sylvester Comprehensive Cancer Center, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Seth A
SA
Wander
Dekuang
D
Zhao
Joyce M
JM
Slingerland
D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects
D050760:Cyclin-Dependent Kinase Inhibitor p27