Expression data from MM231 and MM231-FGD5-cas9 breast cancer cells

To identify the differiational genes and pathways in MM231 and MM231-FGD5-cas9, we examined the microarray gene expression profile of MM231 breast cancer cells vs FGD5-cas9 cells. Ectopic expression or activation of EGFR is found in most TNBCs, and EGFR inhibitors can suppress TNBC growth in vitro. However, these agents exhibit limited efficacy in TNBC patients, possibly due to the nonkinase oncogenic functions of EGFR and the compensatory effects of other oncogenic activities following anti-EGFR therapy. Here, we identified a positive correlation between EGFR and FGD5 expression in TNBC samples. FGD5 deletion attenuated TNBC initiation and progression by decreasing EGFR stability and expression. Moreover, the proteins involved in mutual compensation of EGFR signaling were significantly downregulated in FGD5-deleted TNBC cells. Mechanistically, FGD5 interacted with EGFR to maintain EGFR stability by impeding EGFR ubiquitylation and degradation mediated by the E3 ligase ITCH; disrupting the FGD5-EGFR interaction accelerated EGFR degradation and produced robust anti-TNBC activity. Our study shows that targeted degradation of EGFR through disrupting the FGD5-EGFR interaction is a promising therapeutic strategy for the TNBC subtype of breast cancer. Total RNA of MM231 and MM231-FGD5-cas9 breast cancer cells were obtained, and RNA quantity and quality were measured by NanoDrop ND-1000. RNA microarrays were performed.