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

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 p...

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Autores principales: Barbhuiya, Mustafa A., Kashyap, Manoj K., Puttamallesh, Vinuth N., Kumar, Rekha Vijay, Wu, Xinyan, Pandey, Akhilesh, Gowda, Harsha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915082/
https://www.ncbi.nlm.nih.gov/pubmed/29719615
http://dx.doi.org/10.18632/oncotarget.24853
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author Barbhuiya, Mustafa A.
Kashyap, Manoj K.
Puttamallesh, Vinuth N.
Kumar, Rekha Vijay
Wu, Xinyan
Pandey, Akhilesh
Gowda, Harsha
author_facet Barbhuiya, Mustafa A.
Kashyap, Manoj K.
Puttamallesh, Vinuth N.
Kumar, Rekha Vijay
Wu, Xinyan
Pandey, Akhilesh
Gowda, Harsha
author_sort Barbhuiya, Mustafa A.
collection PubMed
description 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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spelling pubmed-59150822018-05-01 Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays Barbhuiya, Mustafa A. Kashyap, Manoj K. Puttamallesh, Vinuth N. Kumar, Rekha Vijay Wu, Xinyan Pandey, Akhilesh Gowda, Harsha Oncotarget Research Paper 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. Impact Journals LLC 2018-01-01 /pmc/articles/PMC5915082/ /pubmed/29719615 http://dx.doi.org/10.18632/oncotarget.24853 Text en Copyright: © 2018 Barbhuiya et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Barbhuiya, Mustafa A.
Kashyap, Manoj K.
Puttamallesh, Vinuth N.
Kumar, Rekha Vijay
Wu, Xinyan
Pandey, Akhilesh
Gowda, Harsha
Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
title Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
title_full Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
title_fullStr Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
title_full_unstemmed Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
title_short Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
title_sort identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915082/
https://www.ncbi.nlm.nih.gov/pubmed/29719615
http://dx.doi.org/10.18632/oncotarget.24853
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