Molecular mechanism of auto-translocation of membrane anchored EGFR ligand into the nuclear membrane and its diagnostic application of cancer

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HB-EGF and AREG are synthesized as a membrane-anchored growth factor and expressed at the plasma membrane as pro-forms in normal cells. In some malignant tumor cells in culture, however, proHB-EGF and proAREG trans-locate at the ER/nuclear membrane, which endows resistance for anti-cancer drugs. In this study, we established mouse models bearing tumor expressing proAREG auto-translocation mutant, and showed that the tumor acquired resistance for chemotherapy in vivo. We also tried to identify C-terminal processing proteases of proHB-EGF and proAREG.