EGFRis a transmembrane receptor tyrosine kinase involved in regulating cell proliferation, differentiation and survival. EGFR is actively pursued as a therapeutic target because its aberrant expression or activity has been reported in several cancers. Several studies have reported the nuclear localization of the EGFR in various cell types, however, its exact nuclear functions are not clear yet. In this study, we have generated GFP fusion constructs of EGFR and its mutants to analyze their subcellular localizationin normal and cancer cells and impact of its sub-cellular location on its various activities using immunoblotting, confocal microscopy, reporter assays, loss-of-function EGFR mutants, and EGFR specific small molecule inhibitors. We show that EGFR is involved in modulating TCF dependent β-catenin transcriptional activity in HepG2 cells in a similar fashion as IGF1R tyrosine kinase. Moreover, we show that cytoplasmic and nuclear functions are two independent activities of EGFR.

EGFR 是一种参与调节细胞增殖、分化和存活的跨膜受体酪氨酸激酶。EGFR 作为治疗靶标受到积极追捧，因为其异常表达或活性已在多种癌症中得到报道。一些研究报道了 EGFR 在各种细胞类型中的核定位，然而，其确切的核功能尚不清楚。在这项研究中，我们生成了 EGFR 及其突变体的 GFP 融合构建体，以使用免疫印迹、共聚焦显微镜、报告分析、功能丧失分析它们在正常细胞和癌细胞中的亚细胞定位及其亚细胞定位对其各种活动的影响EGFR 突变体和 EGFR 特异性小分子抑制剂。我们表明 EGFR 以与 IGF1R 酪氨酸激酶类似的方式参与调节 HepG2 细胞中依赖于 TCF 的 β-连环蛋白转录活性。此外，我们表明细胞质和细胞核功能是 EGFR 的两个独立活动。