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

[esophageal squamous cell carcinoma]

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 suggests 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 pre-requisite 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 1 A 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 A 2 (EPHA 2 ), a receptor tyrosine kinase was hyperphosphorylated in all the ESCC cell lines used in the study . EPHA 2 is reported to be oncogenic in several cancers and is also known to promote metastasis . Immunohistochemistry based studies have revealed EPHA 2 is overexpressed in nearly 50 % of ESCC . We demonstrate EPHA 2 as a potential therapeutic target in ESCC by carrying out siRNA based knockdown studies . Knockdown of EPHA 2 in ESCC cell line TE 8 resulted in significant decrease in cell proliferation and invasion suggesting it is a promising therapeutic target in ESCC that warrants further evaluation . This article is protected by copyright . All rights reserved .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated