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

Mustafa A. Barbhuiya, Manoj K. Kashyap, Vinuth N. Puttamallesh, Rekha Vijay Kumar, Xinyan Wu, Akhilesh Pandey, Harsha Gowda

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)18422-18434
Number of pages13
JournalOncotarget
Volume9
Issue number26
DOIs
StatePublished - Apr 1 2018

Fingerprint

Protein Array Analysis
Therapeutics
Cell Line
Phase II Clinical Trials
Syk Kinase
Esophageal Squamous Cell Carcinoma
Hematologic Neoplasms
Esophageal Neoplasms
Iran
Heterografts
Small Interfering RNA
India
China
Neoplasms
Proteins
Phosphotransferases
Epithelial Cells
Pharmacology
Growth

Keywords

  • Entospletinib
  • ESCC
  • RPPA
  • SYK

ASJC Scopus subject areas

  • Oncology

Cite this

Barbhuiya, M. A., Kashyap, M. K., Puttamallesh, V. N., Kumar, R. V., Wu, X., Pandey, A., & Gowda, H. (2018). Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays. Oncotarget, 9(26), 18422-18434. https://doi.org/10.18632/oncotarget.24853

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.

In: Oncotarget, Vol. 9, No. 26, 01.04.2018, p. 18422-18434.

Research output: Contribution to journalArticle

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. In: Oncotarget. 2018 ; Vol. 9, No. 26. pp. 18422-18434.
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