下调和上调
表皮生长因子受体
埃罗替尼
癌症研究
酪氨酸激酶
癌细胞
细胞生物学
信号转导衔接蛋白
癌症
表皮生长因子
化学
生物
信号转导
受体
生物化学
基因
遗传学
作者
Jangho Jeong,Ye Eun Hwang,Minwoo Lee,Seula Keum,Seongeun Song,Jung‐Woong Kim,Jee‐Hye Choi,Sangmyung Rhee
摘要
Matrix stiffness has been shown to play a critical role in cancer progression by influencing various cellular processes, including epidermal growth factor (EGF) signaling. However, the underlying molecular mechanisms are not fully understood. Here, we investigated the role of adaptor-related protein complex 1 subunit sigma 1 (AP1S1), a component of adaptor protein complex-1, in the regulation of EGF receptor (EGFR) intracellular trafficking during cancer cell progression. We found that AP1S1 expression was upregulated under stiff matrix conditions, resulting in the regulation of EGFR trafficking in non-small cell lung adenocarcinoma cells. Knockout of AP1S1 caused the lysosomal degradation of EGFR, leading to suppressed EGF-induced anaplastic lymphoma receptor tyrosine kinase phosphorylation. In addition, the downregulation of AP1S1 increased the sensitivity of H1975 cancer cells, which are resistant to tyrosine kinase inhibitors, to erlotinib. Collectively, our results suggest that AP1S1 could regulate EGFR recycling under stiff matrix conditions, and AP1S1 inhibition could be a novel strategy for treating cancer cells resistant to EGFR-targeted anticancer drugs.
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