Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
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Mustafa A. Barbhuiya1,2, Manoj K. Kashyap3, Vinuth N. Puttamallesh4,5, Rekha Vijay Kumar6, Xinyan Wu1, Akhilesh Pandey1,2,4,7,8,9,10 and Harsha Gowda4,10
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3School of Life and Allied Health Sciences, Glocal University, Saharanpur, India
4Institute of Bioinformatics, International Technology Park, Bangalore, India
5Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
6Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, India
7Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
8Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
9Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
10Manipal Academy of Higher Education (MAHE), Manipal, India
Harsha Gowda, email: [email protected]
Akhilesh Pandey, email: [email protected]
Keywords: ESCC; SYK; entospletinib; RPPA
Received: August 31, 2017 Accepted: March 06, 2018 Published: April 06, 2018
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.
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