Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
Cancer Discov. 2013 Jun;3(6):613-5. doi: 10.1158/2159-8290.CD-13-0193.
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.
班和同事们报告了 GSK-3α 的一个新角色，它是连接致癌 KRAS 与胰腺癌细胞中经典和非经典 NF-κB 激活途径的关键，而不是研究得较多的 GSK-3β。虽然它促进非经典激活的机制尚不清楚，但作者表明 GSK-3α 结合并稳定了 TAK1-TAB 复合物，从而持续激活经典 NF-κB 信号。因此，抑制 GSK-3α 会减缓胰腺癌细胞在体外和体内的生长，从而揭示了这种相对研究较少的激酶作为治疗 KRAS 阳性胰腺癌的潜在治疗靶点。
