Figure 7. Targeting WNT signaling disrupts prostate cancer metastasis.

(A) Growth assay of indicated mouse prostate cancer cell lines or primary murine fibroblasts treated with 1μM of tankyrase inhibitor G007-LK for 72 hours (n=2–3; error bars, mean ± s.e.m; One-way ANOVA). Growth is relative to treatment with vehicle control.

(B) Frequency of metastases in prostate tumor-bearing MPApc EPO-GEMM mice after treatment with the tankyrase inhibitor G007-LK (30 mg/kg body weight) or vehicle control (one-sided Fisher’s exact test).

(C) Kaplan-Meier survival curve of prostate tumor-bearing MPApc EPO-GEMM mice treated as in (B) (log-rank test).

(D) Schematic of in vivo metastasis formation assay. MPApc prostate cancer cell lines were tail vein injected into Nu/Nu (Nude) mice and treatment with G007-LK or vehicle control initiated on the same day.

(E) Representative images of H&E stained livers isolated from mice after tail vein injection of MPApc prostate cancer cell lines and treatment with G007-LK (30mg/kg body weight) or vehicle control for 6 weeks (N, normal liver; T, tumor nodules).

(F) Frequency of liver metastases in mice after tail vein injection of MPApc prostate cancer cell lines and treatment as in (E) (one-sided Fisher’s exact test).

(G) Schematic of orthotopic transplantation assay. MP WNT^hi prostate cancer cells harboring a WNT reporter construct (7TCF-luciferase) were orthotopically transplanted into C57BL/6 mice. Treatment with G007-LK or vehicle control was initiated upon confirmation of tumor formation by luciferase imaging.

(H) Representative images of H&E stained livers isolated from mice after orthotopic injection of MP WNT^hi prostate cancer cells and treatment with G007-LK (30mg/kg body weight) or vehicle control for 4 weeks. N, normal liver. Arrows, metastatic tumor nodules.

(I) Number of metastatic liver nodules in mice after orthotopic injection of MP WNT^hi prostate cancer cells and treatment as in (H) (n=9–10; error bars, mean ± s.e.m; two-tailed Mann-Whitney test).