Stress-induced endocytosis and degradation of epidermal growth factor receptor are two independent processes.
Stress-induced endocytosis and degradation of epidermal growth factor receptor are two independent processes.
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DOI：
10.1186/s12935-016-0301-x
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发表时间：
2016
影响因子：
5.8
通讯作者：
Lin Q
中科院分区：
文献类型：
--
作者：
Peng K;Dai Q;Wei J;Shao G;Sun A;Yang W;Lin Q
表皮生长因子受体（EGFR）是一种重要的致癌蛋白，在多种类型的癌症。表皮生长因子受体（EGFR）的内吞和降解是下调细胞表面EGFR水平和调节EGFR信号传导的两个关键步骤。应激条件诱导EGFR的配体非依赖性内吞和降解。然而，目前尚不清楚是否胁迫诱导的内吞和降解是必然的或两个独立的事件。使用免疫印迹和免疫荧光染色测定法测定宫颈癌HeLa细胞中EGFR响应于应激处理的内吞和降解以及p38抑制剂、Caspase-3抑制剂和蛋白酶体抑制剂的作用。应激条件，如蛋白质生物合成抑制，紫外线照射，和高渗透，诱导配体非依赖性的内吞和EGFR的降解。应激诱导的EGFR内吞作用依赖于p38激酶活性，而应激诱导的EGFR降解由Caspase-3活性催化。抑制p38激酶仅损害内吞作用而不损害降解，而抑制胱天蛋白酶-3导致与抑制p38相反的效果。此外，蛋白酶体活性是应激诱导的EGFR降解和细胞死亡所必需的，但不是内吞作用所必需的。结果表明，应激诱导的内吞和降解是两个独立的事件，并表明应激信号可能利用双安全机制下调癌细胞中的细胞表面EGFR。
Epidermal growth factor receptor (EGFR) is an important oncogenic protein in multiple types of cancer. Endocytosis and degradation of epidermal growth factor receptor (EGFR) are two key steps for down-regulation of cell surface level of EGFR and modulation of EGFR signaling. Stress conditions induce ligand-independent endocytosis and degradation of EGFR. However, it is not clear whether stress-induced endocytosis and degradation are consequential or two independent events. Endocytosis and degradation of EGFR in response to stress treatment and effects of the p38 inhibitor, the Caspase-3 inhibitor and the proteasomal inhibitor in cervical cancer HeLa cells were determined using immunoblotting and immunofluorescent staining assays. Stress conditions, such as protein biosynthesis inhibition, UV light irradiation, and hyper-osmosis, induced both ligand-independent endocytosis and degradation of EGFR. Stress-induced endocytosis of EGFR relies on p38 kinase activity, while stress-induced degradation of EGFR is catalyzed by Caspase-3 activity. Inhibiting p38 kinase impairs only the endocytosis but not the degradation, while inhibiting Caspase-3 results in the opposite effect to inhibiting p38. Furthermore, proteasomal activity is required for stress-induced degradation of EGFR and cell death, but not for endocytosis. The results indicate that stress-induced endocytosis and degradation are two independent events and suggest stress signaling may utilize a double-secure mechanism to down-regulate cell surface EGFR in cancer cells.