title: A new alpha in line between KRAS and NF-κB activation?
abstract: Bang and colleagues report a novel role for GSK-3α, rather than the well-studied GSK-3β, as the link between oncogenic KRAS and the canonical and noncanonical activation pathways of NF-κB in pancreatic cancer. Although the mechanism through which it promotes noncanonical activation remains unclear, the authors show that GSK-3α binds and stabilizes TAK1-TAB complexes to constitutively activate canonical NF-κB signaling. Consequently, the inhibition of GSK-3α retards pancreatic cancer growth in vitro and in vivo, thereby revealing this relatively less-studied kinase as a potential therapeutic target for treatment of KRAS-positive pancreatic cancer.
authors.affiliation: Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Chorom
authors.initials: C
authors.lastname: Pak
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
chemical_list: C117307:KRAS protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins