Fig. 8.

IDO1 and COL12A1 synergistically promote GC metastasis. a Cancer cells were inoculated in foot-pad of nude mice to establish xenografted tumor metastasis model. b After inoculation with HGC-27_NC, HGC-27_shCOL12A1, HGC-27_IDO1 and HGC-27_IDO1_shCOL12A1 in nude mice foot-pad for 3 weeks, popliteal lymph nodes (left) were removed and their volumes (right) were measured. c IHC staining of GFP was performed to assess metastatic lymph node ratio in different groups (χ² test). d IHC staining of IDO1, COL12A1 and p-ERK in primary foot pad tumors. e A positive feedback between IDO1 and COL12A1 to promote GC metastasis. Both IDO1-kynurenine and COL12A1-integrin β1 could activate MAPK pathway, which promoted IDO1 and COL12A1 transcriptional activation. The feedback would powerfully enhance GC cell metastasis. “*” represented comparing with “NC” group. *P < 0.05, **P < 0.01, ***P < 0.001. “#” represented comparing with “IDO1” group. ^#P < 0.05, ^##P < 0.01, ^###P < 0.001