Figure 7.

SGCE promotes metastasis of breast cancer cells and drug resistance‐targeted EGFR. A) Immunoblotting analysis of SGCE in gefitinib‐resistant and parental cell lines. Drug sensitivity experiment following SGCE knockdown in B) gefitinib‐resistant HCC1806 and C) MDA‐MB‐231 cell lines. D,E) Migration and invasion abilities of HCC1806 and MDA‐MB‐231 cells following SGCE knockdown and statistical results. F) Luciferase signal intensities in mice after tail‐vein injection with MDA‐MB231 cells expressing indicated constructs and HE‐staining of lungs. G) Working model: In ALDH⁺CD24^lowCD44^high BCSCs, SGCE is highly expressed to maintain stemness, metastasis, chemotherapy, and EGFRi resistance. When SGCE is knocked down, the interaction between SGCE and c‐Cbl is disturbed, and c‐Cbl is free to bind to EGFR, leading to EGFR lysosomal degradation and downregulation of AKT pathway as well as ECM deposition and remodeling. These effects make breast cancer cells sensitive to chemotherapy and EGFRi. (*) P < 0.05; (**) P < 0.01.