Figure 7. WNT/β-catenin signaling increases ROR1 in vivo and primes for noncanonical Wnt signaling.

A-C, VCaP cells were treated with control or APC siRNA for 3 days followed by stimulation with WNT5a for 6 hours and immunoblotting or qRT-PCR. A and B, show p-Smad and p-CAMKII responses to WNT5a with increased ROR1 (representative of at least 3 replicates). C, qRT-PCR confirming APC depletion and showing that WNT5a is not increasing canonical Wnt/β-catenin target genes. D, Representative images of H&E and WLS IHC from multiple metastatic sites in ENZ-resistant rapid autopsy case. E, Representative image of WLS IHC from PDX BIDPC5 (BID5) generated from the case in (D). F, Growth curves of PDX treated with vehicle (black, n=3), ENZ (green, n=3), or ETC-159 (red, n=9). Statistics: Mann-Whitney test compared the difference between the ETC-159 and control arms. G, WNT/β-catenin effectors in response to PORCN inhibition compared with untreated controls from tumors collected at the treatment endpoints.