TNKS inhibition antagonizes canonical Wnt signaling in lung cancer. (A) Immunoblots for Wnt pathway components axin 1, TNKS1, and TNKS2 are shown in ED1 (left panel) and ED2 (right panel) murine lung cancer cell lines following 3 days treatment with TNKS inhibitors or vehicle. (B) Immunoblots are shown for Wnt pathway components, as in panel A, in A549 (left panel) and Hop62 (right panel) human NSCLC cell lines following 3 days treatment with TNKS inhibitors or vehicle. (C) Dose-response of Wnt pathway component stabilization is shown in ED1L cells following 3 days treatment with TNKS inhibitors or vehicle at doses shown. (D) Activity of a lentiviral Wnt-responsive luciferase construct stably expressed in the ED1 cell line was measured following 16 hours cotreatment with TNKS inhibitors and a Wnt activator: 20 mM LiCl (left panel) or 25 ng/mL recombinant murine Wnt3a (right panel). Luciferase activity was normalized to total protein concentrations in each sample and compared to vehicle control. Error bars represent SD of three experiments in triplicate. (* p ≤ 0.05).
Busch et al. BMC Cancer 2013 13:211 doi:10.1186/1471-2407-13-211