Fig. 5
From: mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential
RON mutants show differential spontaneous metastatic potential in vivo. a Graph shows quantification of overall spontaneous metastasis in NOD/SCID mice following transplantation of T47D cells expressing different RON mutants. *P < 0.05, ***P < 0.0005 (Chi-square analysis, Fisher’s exact test). The table on the right summarizes differential activation of signaling pathways in different RON mutants compared to the RON-WT based on in vitro biochemical characterization. b Representative bioluminescence ex-vivo images of different organs from NOD/SCID mice bearing tumors from RON mutants. T47D-Luc-RON WT and mutants were orthotopically injected (5 × 106 cells) into NOD/SCID mice. Tumors were harvested when they reached approximately 1300 mm3, and different organs were analyzed for metastasis by IVIS imaging. (See Supplementary Table S2 for animal numbers, tumor size and tissue tropism of metastasis in each group.) c Representative IHC staining for metastatic RON-Mut A and non-metastatic RON-Mut D. Staining for H&E, human-specific pan-cytokeratin CAM5.2, RON and pS6 (Ser 235/236) is shown for metastatic lung and primary tumor of RON-Mut A, and primary tumor of RON-Mut D. Scale bars represent 100 μm. See also Supplementary Figures S8 and S9. Li liver, Lu lung, Sp spleen, Ov ovary, Ki kidney, Br brain, LN lymph nodes
