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

Nazia Syed, Mustafa A. Barbhuiya, Sneha M. Pinto, Raja Sekhar Nirujogi, Santosh Renuse, Keshava K. Datta, Aafaque Ahmad Khan, Kotteazeth Srikumar, T. S Keshava Prasad, M. Vijaya Kumar, Rekha Vijay Kumar, Aditi Chatterjee, Akhilesh Pandey, Harsha Gowda

Research output: Contribution to journalArticle

Abstract

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 suggest 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 prerequisite 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-1A 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 A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry-based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA-based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation.

Original languageEnglish (US)
Pages (from-to)374-382
Number of pages9
JournalProteomics
Volume15
Issue number2-3
DOIs
StatePublished - Jan 1 2015

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Ephrin-A2
Eph Family Receptors
Phosphotyrosine
Cells
Cell Line
Neoplasms
Therapeutics
Protein-Tyrosine Kinases
Esophageal Squamous Cell Carcinoma
Epithelial Cells
Phosphopeptides
Chemotherapy
Cell proliferation
Receptor Protein-Tyrosine Kinases
Surgery
Small Interfering RNA
Tumors

Keywords

  • Biomedicine
  • In vivo labeling
  • Mass spectrometry
  • Post-translational modifications

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Syed, N., Barbhuiya, M. A., Pinto, S. M., Nirujogi, R. S., Renuse, S., Datta, K. K., ... Gowda, H. (2015). Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma. Proteomics, 15(2-3), 374-382. https://doi.org/10.1002/pmic.201400379

Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma. / Syed, Nazia; Barbhuiya, Mustafa A.; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Renuse, Santosh; Datta, Keshava K.; Khan, Aafaque Ahmad; Srikumar, Kotteazeth; Prasad, T. S Keshava; Kumar, M. Vijaya; Kumar, Rekha Vijay; Chatterjee, Aditi; Pandey, Akhilesh; Gowda, Harsha.

In: Proteomics, Vol. 15, No. 2-3, 01.01.2015, p. 374-382.

Research output: Contribution to journalArticle

Syed, N, Barbhuiya, MA, Pinto, SM, Nirujogi, RS, Renuse, S, Datta, KK, Khan, AA, Srikumar, K, Prasad, TSK, Kumar, MV, Kumar, RV, Chatterjee, A, Pandey, A & Gowda, H 2015, 'Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma', Proteomics, vol. 15, no. 2-3, pp. 374-382. https://doi.org/10.1002/pmic.201400379
Syed, Nazia ; Barbhuiya, Mustafa A. ; Pinto, Sneha M. ; Nirujogi, Raja Sekhar ; Renuse, Santosh ; Datta, Keshava K. ; Khan, Aafaque Ahmad ; Srikumar, Kotteazeth ; Prasad, T. S Keshava ; Kumar, M. Vijaya ; Kumar, Rekha Vijay ; Chatterjee, Aditi ; Pandey, Akhilesh ; Gowda, Harsha. / Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma. In: Proteomics. 2015 ; Vol. 15, No. 2-3. pp. 374-382.
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AU - Syed, Nazia

AU - Barbhuiya, Mustafa A.

AU - Pinto, Sneha M.

AU - Nirujogi, Raja Sekhar

AU - Renuse, Santosh

AU - Datta, Keshava K.

AU - Khan, Aafaque Ahmad

AU - Srikumar, Kotteazeth

AU - Prasad, T. S Keshava

AU - Kumar, M. Vijaya

AU - Kumar, Rekha Vijay

AU - Chatterjee, Aditi

AU - Pandey, Akhilesh

AU - Gowda, Harsha

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N2 - 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 suggest 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 prerequisite 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-1A 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 A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry-based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA-based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation.

AB - 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 suggest 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 prerequisite 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-1A 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 A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry-based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA-based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation.

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