Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays

Abstract

The vast majority of esophageal cancers in China, India and Iran are esophageal squamous cell carcinomas (ESCC). A timely diagnosis provides surgical removal as the main therapeutic option for patients with ESCC. Currently, there are no targeted therapies available for ESCC. We carried out reverse phase protein array-based protein expression profiling of seven ESCC-derivedcell lines and a non-neoplastic esophageal epithelial cell line (Het-1A) to identify differentially expressed proteins in ESCC. SYK non-receptortyrosine kinase was overexpressed in six out of seven ESCC cell lines that were used in the study. We evaluated the role of SYK in ESCC using the pharmacological inhibitor entospletinib (GS-9973) and siRNA-based knock down studies. Entospletinib is a selective inhibitor of SYK, which is currently being evaluated in phase II clinical trials for hematological malignancies. Using in vivo subcutaneous tumor xenografts in mice, we demonstrate that treatment with entospletinib significantly inhibits tumor growth. Further clinical studies are needed to prove the efficacy of entospletinib as a targeted therapeutic agent for treating ESCC.

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

“…To better understand the mechanisms by which C-PAC or AFG inhibit viability of JHAD1 and OE19 EAC cells, we utilized RPPA technology to simultaneously interrogate 304 antibodies to proteins, many implicated in cancer [ 30 , 31 , 32 ]. JHAD1 and OE19 cells were treated with either C-PAC (75 µg/mL) or AFG (400 µg/mL) for 24 h and collected lysates probed with validated antibodies.…”