Fig 2: A proposed model for SHE and ABL signaling during vascular tubulogenesis.Activated ABL promotes enlarged vascular lumen through a downstream effector P-CRKL which increases endothelial cell proliferation and increases Cldn5 expression, thus affecting tight junctions and cell adhesion. Activated ABL phosphorylates SHE, which then interacts with ABL to dampen its activity resulting in the lumen of appropriate size.

Fig 3: Imatinib increases un-phosphorylated (active form) CRKL in HBMECs. (A) Western blot shows decreased expressions of pCRKL in HBMECs after imatinib treatment. (B) Statistical analysis of total and phosphorylated CRKL indicates that the protein level of total CRKL is not affected by imatinib treatment (p > 0.21, linear mixed model ANOVA test), while pCRKL level is significantly reduced (* p < 0.006, linear mixed model ANOVA test). (C) Comparison of pCRKL to total CRKL indicates that this ratio is significantly decreased after imatinib treatment (* p < 0.001).

Fig 4: The expressions of BCR-ABL oncoprotein and its downstream signaling molecules were decreased in RFNs treated CML cells. K562 and K562/G01 cells were co-delivered with gRNA-17 plus donor, RFNs-half plus donor, RFNs plus donor, respectively. Proteins were extracted after 60 h of transfection and analyzed by western blot. Expressions of p-BCR-ABL and BCR-ABL were reduced in RFNs plus donor group (a). The activated phospho-CRKL, phospho-ERK and phospho-STAT5 were down-regulated in RFNs plus donor group (b)

Fig 5: Alterations in the cell junction and adhesion network. (A) An altered PPI network involved in cell junction and adhesion functions. Red-dotted rectangle indicates the interaction between CRKL and VEGR1/FLT1. (B) The centrality measure analysis of the contribution of each node to the PPI network. The x-axis is the “diffusion degree score” (see the method) and the y-axis is the nodes (gene symbols) ranked according to their diffusion degree score.