LGR5 and cancer: Because LGR5 has been considered a specific stem cell marker within the hair follicle and intestine60,78, and to validate the MAPKi sensitizing effect of co-inhibition of HDGF and LGR5, we determined the spheroid formation ability in A375 cells and expanded our investigated cancer types to hepatoma and NSCLC cancer cells, which could better illustrate the stemness maintenance property of LGR5.