Disease relevance of EPHA2

• EPHA2-expressing focal cancer also surrounded microvessels in adenomas with focal cancers [1].
• Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer [1].
• Here we studied the role of ECK during melanoma progression [2].
• ECK mRNA was overexpressed in virtually all melanoma lines tested, and levels were significantly higher in cell lines from distant metastases than primary melanomas; melanocytes were negative [2].
• However, EPHA2 overexpression was more prominent in macroscopic type 3 and 4 tumors than in type 1 or 2 advanced gastric cancer [3].

High impact information on EPHA2

• A protein ligand for the ECK receptor protein-tyrosine kinase has been isolated by using the extracellular domain (ECK-X) of the receptor as an affinity reagent [4].
• Most notably, we identified epithelial cell kinase (EphA2) as being one receptor tyrosine kinase expressed and phosphorylated exclusively in the aggressive metastatic melanoma cells [5].
• Here we report increased levels of the EphA2 (ECK) protein tyrosine kinase in clinical specimens and cell models of breast cancer [6].
• Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation: role of epithelial cell kinase (Eck/EphA2) [5].
• Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression [2].

Chemical compound and disease context of EPHA2

• Genetic sequencing of the tyrosine kinase domain of EPHA2 in 22 samples of xenograft enriched pancreatic cancer did not reveal any inactivating mutations [7].

Biological context of EPHA2

• In the gastric cancer cell lines that endogenously expressed EPHA2, stimulation with ephrinA1-Fc led to decreased EPHA2 protein expression and increased EPHA2 phosphorylation [3].
• The syntenic relationship between this chromosome and human chromosome 1 suggests that the human ECK gene maps to the distal short arm of human chromosome 1 (1p) [8].
• PCR screening of a rodent-human somatic cell hybrid panel by ECK-specific primers showed that ECK is indeed localized to human chromosome 1 [8].
• These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier [9].
• We found that ectopic expression of a mutant ECK fails to induce apoptosis in cancer cells [10].

Anatomical context of EPHA2

• In one cell line, TMK1, EPHA2 expression was barely detectable using northern blotting, RT-PCR, and western blotting [3].
• However, EPHA2 amplification was found in 1 of 33 pancreatic cancers corresponding to a lymph node metastasis, indicating EPHA2 genomic amplification may underlie EphA2 overexpression in a minority of patients [7].
• These expression profiles of B61 in epithelial cells of various organs, developing skeletal system and dorsal root ganglia match those of ECK [11].

Associations of EPHA2 with chemical compounds

• PURPOSE: EphA2 (epithelial cell kinase) is a transmembrane receptor tyrosine kinase that has been implicated in oncogenesis [12].
• Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60 [13].
• A Novel Mechanism for p53 to Regulate Its Target Gene ECK in Signaling Apoptosis [10].

Physical interactions of EPHA2

• EPHA2 interacted with both Src and LMW-PTP, and the interactions increased in EPHA2-overexpressing cells [14].

Other interactions of EPHA2

• Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor-induced neovascularization [1].
• Microvessel counts (MVCs) after immunostaining for CD34 were significantly correlated (r = 0.343, P = 0.037) with overexpression of EPHA2 [1].
• Epithelial cell kinase (ECK) is a receptor protein tyrosine kinase, the role of which in melanoma biology is unclear [2].
• ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers [8].
• Additional PCR screening of a regional screening panel for chromosome 1p indicated that ECK is localized to 1p36, distal to FUCA1 [8].

Analytical, diagnostic and therapeutic context of EPHA2

• B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media [2].
• The authors examined the expression of EPHA2 and EFNA1 using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in four gastric cancer cell lines and 49 primary gastric cancer samples, as well as in normal gastric tissue [3].
• Furthermore, fluorescence in situ hybridization analysis with an ECK-specific P1 clone showed that ECK maps proximal to genetic marker D1S228 [8].
• Similarly, ECK protein was detected by immunoblotting in metastatic melanomas but not in normal melanocytes [15].

References