title: New connections between old pathways: PDK1 signaling promotes cellular transformation through PLK1-dependent MYC stabilization.
abstract: Limited understanding of the functional link between multiple oncogenic pathways is a major barrier in the ongoing effort of cancer biologists to design an effective therapeutic approach to treat malignancies characterized by driver oncogenic network signals. In this issue of Cancer Discovery, Tan and colleagues elucidate a novel PDK1-PLK1-MYC signaling pathway connecting two fundamental oncogenic programs, phosphoinositide 3-kinase and MYC. They define the functional role for PDK1-PLK1-MYC signaling in cancer cell survival and tumor formation and show the therapeutic benefit of inhibiting PDK1 and PLK1 pharmacologically in cancer, tackling the most undruggable tumors defined by elevated levels of the MYC oncoprotein.
authors.affiliation: Department of Urology, School of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: John T
authors.initials: JT
authors.lastname: Cunningham
authors.forename: Davide
authors.initials: D
authors.lastname: Ruggero
mesh_terms: D006801:Humans; D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D014411:Neoplastic Stem Cells / Q000502:physiology; D000097869:Polo-Like Kinase 1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D064413:3-Phosphoinositide-Dependent Protein Kinases; D018797:Cell Cycle Proteins; C546842:MTOR protein, human; C489427:MYC protein, human; C578562:PDPK1 protein, human; D000097869:Polo-Like Kinase 1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D058570:TOR Serine-Threonine Kinases