Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Receptor, EphA2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2005

A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis.

Receptor tyrosine kinases of the Eph family are upregulated in several different types of cancer. One family member in particular, the EphA2 receptor, has been linked to breast, prostate, lung and colon cancer, as well as melanoma. However, mechanisms by which EphA2 contributes to tumor progression are far from clear. In certain tumor cell lines, EphA2 receptor is underphosphorylated, raising the question of whether ligand-induced receptor phosphorylation and its kinase activity play a role in oncogenesis. To test directly the role of EphA2 receptor phosphorylation/kinase activity in tumor progression, we generated EphA2 receptor variants that were either lacking the cytoplasmic domain or carrying a point mutation that inhibits its kinase activity. Expression of these EphA2 mutants in breast cancer cells resulted in decreased tumor volume and increased tumor apoptosis in primary tumors. In addition, the numbers of lung metastases were significantly reduced in both experimental and spontaneous metastasis models. Reduced tumor volume and metastasis are not due to defects in tumor angiogenesis, as there is no significant difference in tumor vessel density between wild-type tumors and tumors expressing EphA2-signaling-defective mutants. In contrast, tumor cells expressing the EphA2 mutants are defective in RhoA GTPase activation and cell migration. Taken together, these results suggest that receptor phosphorylation and kinase activity of the EphA2 receptor, at least in part, contribute to tumor malignancy.

Animals↗
PubMed2006

Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells.

BACKGROUND: The over-expression of the ephrin-A1 ligand receptor EphA2 is associated with the growth and metastatic potential of tumors. Although EphA2 is expressed in a variety of tumors, its expression and function in malignant mesothelioma (MM) remain unknown. The authors hypothesized that expression of the receptor EphA2 in MM cells (MMCs) plays a key role in the growth and haptotactic migration of MM. They also hypothesized that silencing EphA2 expression by using small-interfering RNA (siRNA) inhibits the proliferation and haptotaxis of MMCs and induces apoptosis in MMCs. METHODS: The expression of EphA2 in MMCs and in normal pleural mesothelial cells (PMCs) was studied by using real-time quantitative polymerase chain reaction analysis and Western blot analysis. The growth of MMCs was determined with the WST-1 cell-proliferation assay. The haptotactic migration of MMCs and PMCs was determined with a Boyden chamber assay. Expression of caspases was determined with calorimetric assays. RESULTS: The results demonstrated that silencing the receptor EphA2 by siRNA significantly reduced the proliferation and haptotactic migration of MMCs compared with controls. Over-expression of EphA2 with plasmid pcDNA/EphA2 enhanced the proliferation and haptotaxis of MMCs significantly. Knocking down EphA2 expression initiated caspase-9-mediated apoptosis in MMCs. CONCLUSIONS: The current results suggested that constitutive expression of EphA2 may contribute to the aggressive behavior and cellular survival of MMCs. EphA2 may be an effective therapeutic target in patients with mesothelioma. Silencing the receptor EphA2 gene is a novel approach for the containment of growth and migration of tumor in patients with malignant mesothelioma.

Apoptosis↗
PubMed1999

E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.

EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development. We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.

Breast Neoplasms↗
PubMed2000

The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization.

Eph receptor tyrosine kinases and their ephrin ligands have been implicated in embryonic vascular development and in in vivo models of angiogenesis. Eph proteins may also regulate tumor neovascularization, but this role has not been previously investigated. To screen for Eph proteins expressed in tumor blood vessels, we used tumor xenografts grown in nude mice from MDA-MB-435 human breast cancer cells or KS1767 human Kaposi's sarcoma cells. By immunohistochemistry, the ephrin-A1 ligand and one of its receptors, EphA2, were detected throughout tumor vasculature. Double-labeling with anti-CD34 antibodies demonstrated that both ephrin-A1 and EphA2 were expressed in xenograft endothelial cells and also tumor cells. Furthermore, EphA2 was tyrosine-phosphorylated in the xenograft tumors, indicating that it was activated, presumably by interacting with ephrin-A1. Ephrin-A1 and EphA2 were also detected in both the vasculature and tumor cells of surgically removed human cancers. In an in vitro angiogenesis model, a dominant negative form of EphA2 inhibited capillary tube-like formation by human umbilical vein endothelial cells (HUVECs), demonstrating a requirement for EphA receptor signaling. These data suggest that ephrin-A1 and EphA2 play a role in human cancers, at least in part by influencing tumor neovascularization. Eph proteins may represent promising new targets for antiangiogenic cancer treatments.

Animals↗
PubMed2006

Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation.

Endocytosis of Eph receptors is critical for a number of biological processes, including modulating axon growth cone collapse response and regulating cell surface levels of receptor in epithelial cells. In particular, ephrin-A ligand stimulation of tumor cells induces EphA2 receptor internalization and degradation, a process that has been explored as a means to reduce tumor malignancy. However, the mechanism and regulation of ligand-induced Eph receptor internalization are not well understood. Here we show that SHIP2 (Src homology 2 domain-containing phosphoinositide 5-phosphatase 2) is recruited to activated EphA2 via a heterotypic sterile alpha motif (SAM)-SAM domain interaction, leading to regulation of EphA2 internalization. Overexpression of SHIP2 inhibits EphA2 receptor endocytosis, whereas suppression of SHIP2 expression by small interfering RNA-mediated gene silencing promotes ligand-induced EphA2 internalization and degradation. SHIP2 regulates EphA2 endocytosis via phosphatidylinositol 3-kinase-dependent Rac1 activation. Phosphatidylinositol 3,4,5-trisphosphate levels are significantly elevated in SHIP2 knockdown cells, phosphatidylinositol 3-kinase inhibitor decreases phosphatidylinositol 3,4,5-trisphosphate levels and suppresses increased EphA2 endocytosis. Ephrin-A1 stimulation activates Rac1 GTPase, and the Rac1-GTP levels are further increased in SHIP2 knockdown cells. A dominant negative Rac1 GTPase effectively inhibited ephrin-A1-induced EphA2 endocytosis. Together, our findings provide evidence that recruitment of SHIP2 to EphA2 attenuates a positive signal to receptor endocytosis mediated by phosphatidylinositol 3-kinase and Rac1 GTPase.

Animals↗
PubMed2004

Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist.

Tumor-associated angiogenesis is critical for tumor growth and metastasis and is controlled by various pro- and antiangiogenic factors. The Eph family of receptor tyrosine kinases has emerged as one of the pivotal regulators of angiogenesis. Here we report that interfering with EphA signaling resulted in a pronounced inhibition of angiogenesis in ex vivo and in vivo model systems. Administration of EphA2/Fc soluble receptors inhibited, in a dose-dependent manner, microvessel formation in rat aortic ring assay, with inhibition reaching 76% at the highest dose of 5000 ng/ml. These results were further confirmed in vivo in a porcine aortic endothelial cell-vascular endothelial growth factor (VEGF)/basic fibroblast growth factor Matrigel plug assay, in which administration of EphA2/Fc soluble receptors resulted in 81% inhibition of neovascularization. The additive effects of simultaneous inhibition of VEGF receptor 2 and EphA signaling pathways in aortic ring assay and antiangiogenic efficacy of EphA2/Fc soluble receptors against VEGF/basic fibroblast growth factor-mediated neovascularization in vivo indicated a critical and nonredundant role for EphA signaling in angiogenesis. Furthermore, in two independent experiments, we demonstrated that EphA2/Fc soluble receptors strongly (by approximately 50% versus controls) suppressed growth of ASPC-1 human pancreatic tumor s.c. xenografts. Inhibition of tumor growth was due to decreased proliferation of tumor cells. In an orthotopic pancreatic ductal adenocarcinoma model in mice, suppression of EphA signaling by i.p. administration of EphA2/Fc (30 micro g/dose, three times a week for 56 days) profoundly inhibited the growth of primary tumors and the development of peritoneal, lymphatic, and hepatic metastases. These data demonstrate a critical role of EphA signaling in tumor growth and metastasis and provide a strong rationale for targeting EphA2 receptors for anticancer therapies.

Angiogenesis Inhibitors↗
PubMed2006

Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin.

EphA2 receptor tyrosine kinase is frequently overexpressed in different human cancers, suggesting that it may promote tumor development and progression. However, evidence also exists that EphA2 may possess antitumorigenic properties, raising a critical question on the role of EphA2 kinase in tumorigenesis in vivo. We report here that deletion of EphA2 in mouse led to markedly enhanced susceptibility to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage skin carcinogenesis. EphA2-null mice developed skin tumors with an increased frequency and shortened latency. Moreover, tumors in homozygous knockout mice grew faster and were twice as likely to show invasive malignant progression. Haploinsufficiency of EphA2 caused an intermediate phenotype in tumor development but had little effects on invasive progression. EphA2 and ephrin-A1 exhibited compartmentalized expression pattern in mouse skin that localized EphA2/ephrin-A1 interactions to the basal layer of epidermis, which was disrupted in tumors. Loss of EphA2 increased tumor cell proliferation, whereas apoptosis was not affected. In vitro, treatment of primary keratinocytes from wild-type mice with ephrin-A1 suppressed cell proliferation and inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) activities. Both effects were abolished in EphA2-null keratinocytes, suggesting that loss of ERK inhibition by EphA2 may be one of the contributing mechanisms for increased tumor susceptibility. Interestingly, despite its tumor suppressive function, EphA2 was overexpressed in skin tumors compared with surrounding normal skin in wild-type mice, similar to the observations in human cancers. EphA2 overexpression may represent a compensatory feedback mechanism during tumorigenesis. Together, these results show that EphA2 is a novel tumor suppressor gene in mammalian skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2002

An ephrin mimetic peptide that selectively targets the EphA2 receptor.

Eph receptor tyrosine kinases represent promising disease targets because they are differentially expressed in pathologic versus normal tissues. The EphA2 receptor is up-regulated in transformed cells and tumor vasculature where it likely contributes to cancer pathogenesis. To exploit EphA2 as a therapeutic target, we used phage display to identify two related peptides that bind selectively to EphA2 with high affinity (submicromolar K(D) values). The peptides target the ligand-binding domain of EphA2 and compete with ephrin ligands for binding. Remarkably, one of the peptides has ephrin-like activity in that it stimulates EphA2 tyrosine phosphorylation and signaling. Furthermore, this peptide can deliver phage particles to endothelial and tumor cells expressing EphA2. In contrast, peptides corresponding to receptor-interacting portions of ephrin ligands bind weakly and promiscuously to many Eph receptors. Bioactive ephrin mimetic peptides could be used to selectively deliver agents to Eph receptor-expressing tissues and modify Eph signaling in therapies for cancer, pathological angiogenesis, and nerve regeneration.

Amino Acid Sequence↗
PubMed2005

Inhibition of retinal neovascularization by soluble EphA2 receptor.

Eph receptor tyrosine kinases (RTKs) and their ligands, known as ephrins, play an important role in vascular remodeling during embryogenesis, but their functions in adult angiogenesis are just beginning to be investigated. In this report, we investigated the effect of blocking EphA receptor activation on VEGF-induced angiogenic responses of cultured retinal endothelial cells and on retinal neovascularization in a rodent model of retinopathy of prematurity (ROP). Soluble EphA2-Fc receptors inhibited ephrin-A1 ligand or VEGF-induced BRMEC migration and tube formation without affecting proliferation in vitro. Since EphA2-Fc receptors can inhibit activation of multiple EphA receptors, the specific role of EphA2 receptor in angiogenesis was further investigated in EphA2-deficient endothelial cells. Loss of EphA2 in endothelial cells leads to defective cell migration and assembly in response to either ephrin-A1 or VEGF. Finally, a significant reduction in the severity of abnormal retinal neovascularization was observed in the eyes treated with soluble EphA2-Fc receptors, yet the normal total retinal vascular area was not significantly changed. Because soluble Eph receptor significantly inhibited pathologic retinal angiogenesis without affecting normal intraretinal vessels, it may be a promising agent for treatment of retinal angiogenesis in a number of human ocular diseases.

Animals↗
PubMed2003

High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia.

EphA2 is a transmembrane receptor tyrosine kinase that is overexpressed in many carcinomas. Specific targeting of EphA2 with monoclonal antibodies is sufficient to inhibit the growth, migration and invasiveness of aggressive cancers in animal models. Using immunohistochemical analyses, we measured the expression of EphA2 in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostate tissue from ninety-three radical prostatectomy specimens. These results were related to multiple clinical and pathologicalcharacteristics. The fraction of cells staining positively with EphA2 in benign prostatic epithelium (mean, 12%) was significantly lower than that in high-grade prostatic intraepithelial neoplasia (mean, 67%, P < 0.001) and prostatic adenocarcinoma (mean, 85%, P < 0.001). Moreover, the intensity of EphA2 immunoreactivity in prostatic adenocarcinoma was significantly higher than in benign prostatic tissue (P < 0.001) or high-grade prostatic intraepithelial neoplasia (P < 0.001). Benign prostatic epithelium showed weak or no immunoreactivity for EphA2 in all cases examined. Whereas EphA2 immunoreactivity related to neoplastic transformation, it did not correlate with other clinical and pathological parameters examined. Our data suggest that EphA2 levels increase as prostatic epithelial cells progress toward a more aggressive phenotype. Progressively higher levels of EphA2 in high-grade prostatic intraepithelial neoplasia and prostatic carcinoma are consistent with recent evidence that EphA2 functions as a powerful oncogene. Moreover, the presence of high levels of EphA2 in these cells suggests opportunities for prostate cancer prevention and treatment.

Adenocarcinoma↗
PubMed2003

Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival.

PURPOSE: Underestimation of disease severity is a major problem confronting the successful clinical management of non-small cell lung cancer. Recent advances in molecular biological substaging may provide an opportunity to identify those patients with the most aggressive forms of the disease, but there is a continuing need for accurate markers of disease relapse and survival. EXPERIMENTAL DESIGN: In our present study, immunohistochemical analyses of a retrospective database of pathologic specimens were used to demonstrate that the EphA2 receptor kinase is frequently overexpressed in NSCLC. RESULTS: Initial presentation with high levels of EphA2 predicts subsequent survival, overall relapse, and site of relapse. Specifically, high levels of EphA2 in the primary tumor predict brain metastases, whereas low levels of EphA2 relate to disease-free survival or contralateral lung metastasis. CONCLUSIONS: These data suggest that EphA2 may provide a molecular marker to identify and predict patients who have isolated brain metastases. Moreover, the high levels of EphA2 in lung cancer may provide an opportunity for therapeutic targeting.

Biomarkers, Tumor↗
PubMed2005

EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics.

Eph receptors are a unique family of receptor tyrosine kinases (RTK) that play critical roles in embryonic patterning, neuronal targeting, and vascular development during normal embryogenesis. Eph RTKs and their ligands, the ephrins, are also frequently overexpressed in a variety of cancers and tumor cell lines. In particular, one family member, EphA2, is overexpressed in breast, prostate, lung, and colon cancers. Unlike traditional oncogenes that often function only in tumor cells, recent data show that Eph receptors mediate cell-cell interactions both in tumor cells and in the tumor microenvironment, namely the tumor stroma and tumor vasculature. Thus, EphA2 receptors are attractive targets for drug design, as targeting these molecules could simultaneously inhibit several aspects of tumor progression. This review focuses on the multiple roles of EphA2 in cancer progression, the mechanisms by which EphA2 inhibition may halt this progression, and the pre-clinical results of EphA2 inhibition in various cancer model systems.

Animals↗
PubMed2002

Negative regulation of EphA2 receptor by Cbl.

The c-Cbl proto-oncogene product Cbl has emerged as a negative regulator of receptor and non-receptor tyrosine kinases, a function dependent on its recently identified ubiquitin ligase activity. Here, we report that EphA2, a member of Eph receptor tyrosine kinases is negatively regulated by Cbl. The negative regulation of EphA2 mediated by Cbl is dependent on the activity of EphA2, as the kinase inactive mutant of EphA2 cannot be regulated by Cbl. Moreover, a point mutation (G306E-Cbl) in TKB region of Cbl that has been reported to abolish Cbl binding to RTKs and non-receptor tyrosine kinases impaired the binding to active EphA2. The dominant negative mutant 70Z-Cbl, which has a 17-amino acids deletion in the N-boundary of the RING finger domain, defuncted negative regulatory function of Cbl to EphA2. These results demonstrate that the TKB domain and RING finger domain of Cbl are essential for this negative regulation.

Cell Line↗
PubMed2004

EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation.

Angiogenesis is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Targeted disruption of several EphB class receptor tyrosine kinases results in vascular remodeling defects during embryogenesis. The role of EphA class receptors in vascular remodeling, however, is not well-characterized. We recently demonstrated that global inhibition of EphA receptors disrupts endothelial migration induced by ephrin, VEGF or tumor-derived signals, though the specific target remained undefined. Here, we report that EphA2 regulates endothelial cell assembly and migration through phosphoinositide (PI) 3-kinase-mediated activation of Rac1 GTPase in two model systems: primary bovine and murine pulmonary microvascular endothelial cells. EphA2-deficient endothelial cells fail to undergo vascular assembly and migration in response to ephrin-A1 in vitro. Ephrin-A1 stimulation induces PI3-kinase-dependent activation of Rac1 in wild-type endothelial cells, whereas EphA2-deficient cells fail to activate Rac1 upon stimulation. Expression of dominant negative PI3-kinase or Rac1 inhibits ephrin-A1-induced endothelial cell migration. Consistent with in vitro data, EphA2-deficient mice show a diminished angiogenic response to ephrin-A1 in vivo. Moreover, EphA2-deficient endothelial cells fail to assemble in vivo when transplanted into recipient mice. These data suggest that EphA2 is an essential regulator of post-natal angiogenesis.

Adenoviridae↗
PubMed2006

A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma.

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers.

Brain Neoplasms↗
PubMed2005

The clinical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas.

OBJECTIVES: To examine the expressions of the protein and mRNA of EPHA2 and EphrinA-1 in epithelial ovarian carcinomas/ovarian cancer cell lines and explore their prognostic value. METHODS: To validate the immunohistochemical method, two ovarian cancer cell lines (OVCAR3 and SKOV3) were examined with RT-PCR, Western blot, and immunohistochemistry for EphA2 and EphrinA-1 expressions. Tumors from 118 patients with advanced epithelial ovarian cancer were then evaluated for EPHA2 and Ephrin A-1 protein expression, and frozen tissues from 30 cases were used for laser capture microdissection (LCM) assistant RT-PCR RNA analysis. RESULTS: 11 (9.3%), 67 (56.8%), 26 (22.0%), and 14 (11.9%) tumors demonstrated negative, weak, moderate, and strong EphA2 protein expressions, respectively, while 3 (2.5%), 67 (56.8%), 32 (27.1%), and 16 (13.8%) tumors were negative, weak, moderate, and strong for Ephrin A-1 protein expression, respectively. Variable amount of mRNA expression was observed in the 30 tumors analyzed by the method of LCM assistant RT-PCR. There was a trend for association between higher levels of either EphA2 or Ephrin A-1 expression and higher histological grade (P = 0.05 for both factors). No significant correlation between the expressions of EphA2 or Ephrin A-1 and age, histological type, and FIGO stage was observed. Patients with higher levels of EphA2 protein expressions had significantly shorter survival. Cox multivariate analyses revealed that residual tumor after surgery, histological type, and EphA2 protein expression were of independent prognostic significance. CONCLUSIONS: High level of EphA2 protein expression is significantly associated with a shorter patient survival and EphA2 receptor is a valuable prognostic marker for ovarian carcinoma.

Adult↗
PubMed2006

Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis.

Angiogenesis, the process by which new blood vessels are formed from preexisting vasculature, is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Prior studies from our laboratory demonstrate that the EphA2 receptor tyrosine kinase is a key regulator of angiogenesis in vivo. The EphA receptor-mediated angiogenic response is dependent on activation of Rho family GTPase Rac1 and is regulated by phosphatidylinositol 3-kinase. Here we report the identification of Vav2 and Vav3 as guanine nucleotide exchange factors (GEFs) that link the EphA2 receptor to Rho family GTPase activation and angiogenesis. Ephrin-A1 stimulation recruits the binding of Vav proteins to the activated EphA2 receptor. The induced association of EphA receptor and Vav proteins modulates the activity of Vav GEFs, leading to activation of Rac1 GTPase. Overexpression of either Vav2 or Vav3 in primary microvascular endothelial cells promotes Rac1 activation, cell migration, and assembly in response to ephrin-A1 stimulation. Conversely, loss of Vav2 and Vav3 GEFs inhibits Rac1 activation and ephrin-A1-induced angiogenic responses both in vitro and in vivo. In addition, embryonic fibroblasts derived from Vav2-/- Vav3-/- mice fail to spread on an ephrin-A1-coated surface and exhibit a significant decrease in the formation of ephrin-A1-induced lamellipodia and filopodia. These findings suggest that Vav GEFs serve as a molecular link between EphA2 receptors and the actin cytoskeleton and provide an important mechanism for EphA2-mediated angiogenesis.

Animals↗