Therefore, our results demonstrated that, in HER2+ breast cancer, trastuzumab treatment induced PM-to-ER retrograde transportation of DPAGT1, which protected ADAM10 from ERAD via N-glycosylation, consequently resulting in robust HER2 shedding, trastuzumab resistance, and poor clinical outcomes (Figure 9A). The gene discussed is DPAGT1; the disease is breast cancer.