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. Author manuscript; available in PMC: 2020 May 28.
Published in final edited form as: Cell Rep. 2019 Dec 10;29(11):3421–3434.e8. doi: 10.1016/j.celrep.2019.11.018

Figure 6. AXL and ABL2 tyrosine kinases are required for lung adenocarcinoma metastasis to the brain.

Figure 6.

A) Overall survival (OS) and B) BMFS of mice injected intracardially with PC9-BrM3 cells expressing shSCR (n=16) or shABL2 (n=18). C) OS and D) BMFS of mice injected intracardially with PC9-BrM3 cells expressing shNTC (n=9) or shAXL (n=10). E) Representative images and F) quantification of brain met burden in mice on day 30 post-intracardiac injection of PC9-BrM3 cells expressing shSCR (n=8) or shABL2 (n=8). G) Representative images and H) quantification of brain met burden in mice on day 38 post-intracardiac injection of PC9-BrM3 cells with shNTC (n=10) or shAXL (n=10). I) OS of mice injected intracardially with PC9-BrM3 cells and treated with vehicle (n=18) or 100 mg/kg Q.D. ABL001 (n=20). Drug dosing began 24 h post-intracardiac injection after mice were separated into respective groups. J) Immunoblots of ABL kinase activity (p-CRKL-Y207) in established in vivo brain metastases from six mice injected with H1975 cells and treated with vehicle (n=3) or 100 mg/kg ABL001 (n=3). Mice were treated at 3, 12, and 24 h prior to harvesting brain metastases. K) Quantification of brain flux and whole-body flux in mice on day 7 post-intracardiac injection (pre-dox phase) with PC9-BrM3 cells transduced with inducible shNTC, shAXL or shTAZ. Statistical analysis performed by one-way ANOVA and Fisher post-hoc testing. L) Quantification of brain flux in the indicated mice before and after administering dox water starting on Day 10 (black arrow). Brain flux was normalized to the Day 7 baseline mean for each of the three groups with statistical analysis performed using a mixed-effects model. ** p-value < 0.01. For survival analysis, statistical testing performed by Log-rank (Mantel-Cox).