Fig. 9

Model depicting the mechanism by which ZFP64 induced nab-paclitaxel insensitivity through the targeting of GAL-1. In gastric cancer cells, ZFP64 overexpression promoted the transcription of GAL-1. Increased intracellular GAL-1 levels induce CSC-like properties by activating the MAPK and PI3K/AKT pathways and subsequently inhibiting the uptake of nab-paclitaxel. Meanwhile, GAL-1 was secreted into the extracellular milieu and stimulated T cells to finally induce an immunosuppressive microenvironment. ① Nuclear translocation of ZFP64, ② the expression of GAL-1; ③ GAL-1 activated the MAPK and PI3K signal to induce the stem cell phenotype of GC cells; ④ the stem cell phenotype resulted in decreased endocytosis of chemotherapy drugs; ⑤ the secretion of GAL-1; ⑥ a high level of GAL-1 promoted an immunosuppressive microenvironment