A new alpha in line between KRAS and NF-κB activation?

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.