EGFR and neoplasm: In cells expressing EGFR possessing activating mutation, namely, HCC827 and HCC4006, when treated with TKI, ectopic SHCBP1 expression also increased SHCBP1 nuclear translocation, tumor sphere formation, and TOP/FOP activity, further suggesting that SHCBP1 overexpression-induced nuclear SHCBP1 elevation could also mediate activation of β-catenin signaling activation and increase the malignant properties of tumor cells independent of EGFR activation (Fig. 5f, Supplementary Fig. 5e, f).