Fig. 7.

IGFBP2 is required for EGFR stabilization in FLO1 cells after acidic bile salts treatment. a, FLO1 cells with IGFBP2 knockdown (si-IGFBP2) and control cells (si-control) were treated with or without acidic bile salts (ABS, pH 4, 200 μM) and then recovered in full medium with cycloheximide (CHX, 50 μg/ml) for the indicated time points. Whole cell lysates were used for western blot analysis to determine the half-life time change of EGFR. b, Quantification of relative EGFR protein amounts at different time points (EGFR/β-actin). *** p < 0.001, ** p < 0.01. c, A graphic cartoon summarizing the findings in this study. ABS induces degradation of MiRNAs that targets IGFBP2, leading to upregulation of IGFBP2 and EGFR. IGFBP2 binds to EGFR and stabilizes EGFR protein and promotes EGFR nuclear accumulation. IGFBP2 forms a complex with EGFR and DNA-PKcs. EGFR activates DNA-PKcs to mediate repair of DNA double strand breaks induced by ABS exposure