Fig. 7: The FLAD1/LSD1/SREBP1 pathway is a therapeutic target for TNBC.

a Left: dose–response curves and half maximal inhibition concentration values of GSK-LSD1 in LM2-4175 cells expressing control or FLAD1 shRNA. Right: Bar plot illustrating the mean cell survival rates in LM2-4175 cells expressing control or FLAD1 shRNA treated with 80 µM GSK-LSD1 for 48 h. b Left: dose–response curves and half maximal inhibition concentration values of Fatostatin in LM2-4175 cells expressing control or FLAD1 shRNA. Right: Bar plot illustrating the mean cell survival rates in LM2-4175 cells expressing control or FLAD1 shRNA treated with 10 µM Fatostatin for 48 h. c The results of the cell viability assay in two TNBC patient-derived organoid models treated with 100 µM GSK-LSD1 or 5 µM Fatostatin. Representative bright-field images and cell viability assays are shown. Scale bars, 100 μm. d–f Experimental protocols (d) for animal studies to observe whether FLAD1 expression is associated with GSK-LSD1 and Fatostatin sensitivity. Tumor volume (e) and weight (f) of shCtrl or shFLAD1 LM2-4175 cells in BALB/c nude mice treated with GSK-LSD1 or Fatostatin are presented (6 mice per group). g–i Experimental protocols (g) for animal studies to observe whether GSK-LSD1 could improve sensitivity to doxorubicin. Tumor volume (h) and weight (i) of LM2-4175 cells in BALB/c nude mice treated with GSK-LSD1 and/or doxorubicin are presented (6 mice per group). j–l Experimental protocols (j) for animal studies to observe whether GSK-LSD1 could improve sensitivity to SG. Tumor volume (k) and weight (l) of LM2-4175 cells in NOD-SCID mice treated with GSK-LSD1 or/and SG are presented (6 mice per group). Graph bars represent mean ± SEM, and P value was calculated by two-tailed Student’s t-test. Results in a and b represent biologically independent experiments of n = 5. c, n = 3 independent experiments, a representative example is shown. Source data are provided as a Source Data file. PBS, phosphate buffer saline. SG, sacituzumab govitecan. Doxo, doxorubicin. i.p, intraperitoneal injection. i.v, intravenous injection.