Depletion of ZNRF1 in lung or cervical cancer cells results in decreased EGF-induced EGFR ubiquitination and increased accumulation of EGFR in the early endosomes, which eventually impedes EGFR degradation and leads to prolonged activation of AKT and extracellular signal-regulated kinase (ERK) signaling. Here, EGFR is linked to cervical cancer.