文章基本信息

标题：Activation of EPHA2-ROBO1 Heterodimer by SLIT2 Attenuates Non-canonical Signaling and Proliferation in Squamous Cell Carcinomas
本地全文：下载
作者：Saumya Srivastava ; Ka Ming Pang ; Mari Iida 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：11
页码：1-35
DOI：10.1016/j.isci.2020.101692
语种：English
出版社：Elsevier
摘要：SummaryThe tyrosine kinase receptor ephrin receptor A2 (EPHA2) is overexpressed in lung (LSCC) and head and neck (HNSCC) squamous cell carcinomas. Although EPHA2 can inhibit tumorigenesis in a ligand-dependent fashion via phosphorylation of Y588 and Y772, it can promote tumorigenesis in a ligand-independent manner via phosphorylation of S897. Here, we show that EPHA2 and Roundabout Guidance Receptor 1 (ROBO1) interact to form a functional heterodimer. Furthermore, we show that the ROBO1 ligand Slit Guidance Ligand 2 (SLIT2) and ensartinib, an inhibitor of EPHA2, can attenuate growth of HNSCC cells and act synergistically in LSCC cells. Our results suggest that patients with LSCC and HNSCC may be stratified and treated based on their EPHA2 and ROBO1 expression patterns. Although ~73% of patients with LSCC could benefit from SLIT2+ensartinib treatment, ~41% of patients with HNSCC could be treated with either SLIT2 or ensartinib. Thus, EPHA2 and ROBO1 represent potential LSCC and HNSCC theranostics.Graphical AbstractDisplay OmittedHighlights•EPHA2 heterodimerizes with ROBO1 in LSCC and HNSCC•SLIT2 inhibits non-canonical signaling and cellular proliferation in SCCs•SLIT2 is a potential therapeutic and EPHA2 and ROBO1 are potential theranosticsBiological Sciences; Cell Biology; Molecular Biology; Cancer Systems Biology