Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used as a treatment for non-small cell lung cancer. There have been some reports of EGFR-TKIs being associated with vascular adverse events. We found that EGFR-TKIs decreased the proliferation of HMEC-1 (immortalized human dermal microvascular endothelial cells) and HMVEC (human dermal microvascular endothelial cells), and also inhibited the phosphorylation of EGFR and ERK. We examined the mRNA expression profile of erlotinib-treated HMEC-1 s and identified IQ motif containing GTPase activating protein 1 (IQGAP1) as the most consistently upregulated transcript and protein. IQGAP1 was also over-expressed and colocalized with endothelial cells in the lesional skin. Notably, increased IQGAP1 expression was associated with decreased transendothelial electrical resistance and increased vascular permeability in vitro. Erlotinib treatment enriched the staining of IQGAP1 and reduced the intensities of α-catenin at the sites of cell-cell contact. In conclusion, erlotinib induces adherens junction dysfunction by modulating the expression of IQGAP1 in dermal endothelial cells. This article is protected by copyright. All rights reserved.

中文翻译：

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由 EGFR 酪氨酸激酶抑制剂诱导的紫癜性药疹与 IQGAP1 介导的血管通透性增加有关。

表皮生长因子受体酪氨酸激酶抑制剂 (EGFR-TKI) 用于治疗非小细胞肺癌。有一些报道称 EGFR-TKI 与血管不良事件有关。我们发现 EGFR-TKI 降低了 HMEC-1（永生化人真皮微血管内皮细胞）和 HMVEC（人真皮微血管内皮细胞）的增殖，并且还抑制了 EGFR 和 ERK 的磷酸化。我们检查了厄洛替尼处理的 HMEC-1 的 mRNA 表达谱，并确定含有 GTP 酶激活蛋白 1 (IQGAP1) 的 IQ 基序是最一致上调的转录物和蛋白质。IQGAP1 也过表达并与损伤皮肤中的内皮细胞共定位。尤其，IQGAP1 表达增加与体外跨内皮电阻降低和血管通透性增加有关。厄洛替尼处理丰富了 IQGAP1 的染色并降低了细胞 - 细胞接触部位的 α-连环蛋白的强度。总之，厄洛替尼通过调节真皮内皮细胞中 IQGAP1 的表达来诱导粘附连接功能障碍。本文受版权保护。版权所有。