Fig. 6

GRK3 promoted tumor growth, while inhibition of GRK3 by LD2 significantly suppressed GAC growth in xenografts. A Representative tumor images and tumor volume were shown in MKN45 GRK3 overexpression (OE) vs negative control group (NC) over three-week period after implantation. B-D Tumor burden, tumor weights and tumor volumes were shown at end point. E GRK3 level was detected by qPCR in treated tumor tissues compared to NC group. ***P < 0.001. F Co-immunofluorescent staining of GRK3 and SOX9 was performed in tumors of GRK3 OE group vs NC group. Representative images were shown. Scale bar: 25µm. G Representative GA0518 xenograft tumors in LD2 treatment group vs control were shown after 2-week treatment. H & I tumor weights (H) and tumor volumes (I) were significantly reduced in the LD2-treated group compared with that of the control group. *P < 0.01; **P < 0.001. J Mouse body weight was measured in the indicated group. K Immunofluorescent staining of GRK3, YAP1, SOX9 and proliferation marker Ki67 was performed in LD2 treated tumor tissues compared with control tumor tissues. Images were captured by confocal microscopy. Scale bar: 25µm. L Diagram demonstrates the link between GRK3 and YAP1 and its downstream targets. Novel GRK3 inhibitor LD2 can curtail tumor cell progression and metastases mediated by the GRK3-YAP1 axis