Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous cell carcinoma.

[esophageal squamous cell carcinoma]

Esophageal squamous cell carcinoma (ESCC ) is one of the most common malignancies in Asia . Currently , surgical resection of early stage tumor is the best available treatment . However , most patients present late when surgery is not an option . Data suggests that chemotherapy regimens are inadequate for clinical management of advanced cancer . Targeted therapy has emerged as one of the most promising approaches to treat several malignancies . A pre-requisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies . We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non-neoplastic Het 1 A cell line to identify activated tyrosine kinase signaling pathways in ESCC . A total of 278 unique phosphopeptides were identified across these cell lines . This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC . Ephrin receptor A 2 (EPHA 2 ), a receptor tyrosine kinase was hyperphosphorylated in all the ESCC cell lines used in the study . EPHA 2 is reported to be oncogenic in several cancers and is also known to promote metastasis . Immunohistochemistry based studies have revealed EPHA 2 is overexpressed in nearly 50 % of ESCC . We demonstrate EPHA 2 as a potential therapeutic target in ESCC by carrying out siRNA based knockdown studies . Knockdown of EPHA 2 in ESCC cell line TE 8 resulted in significant decrease in cell proliferation and invasion suggesting it is a promising therapeutic target in ESCC that warrants further evaluation . This article is protected by copyright . All rights reserved .