Ephrin-A1 is a negative regulator in glioma through down-reguation of EphA2 and FAK

Liu, Dong Ping; Yan, Wang; Koeffler, H. Phillip; Xie, Dong

doi:10.3892/ijo.30.4.865

Cited by 36 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results demonstrated that EphA2 signaling through FAK can promote cellular adhesion and invasion. Similar results were recently reported by Liu and colleagues, who observed that forced expression of ephrin-A1 in glioma cell lines resulted in the degradation of EphA2 concomitant with a downregulation of FAK resulting in an inhibition of cellular migration, proliferation, and anchorage independent growth (Liu et al, 2007). Collectively, these studies suggest that signaling through EphA2 and ephrin-A1 can result in either promotion or inhibition of cellular adhesion, migration, and invasion depending on the cell type.…”

Section: Focal Adhesion Kinase Signaling As a Mediator Of Melanoma Vmsupporting

confidence: 76%

Deciphering the signaling events that promote melanoma tumor cell vasculogenic mimicry and their link to embryonic vasculogenesis: Role of the Eph receptors

Hess

Margaryan

Seftor

et al. 2007

Developmental Dynamics

View full text Add to dashboard Cite

During embryogenesis, the primordial microcirculation is formed through a process known as vasculogenesis. The term "vasculogenic mimicry" has been used to describe the manner in which highly aggressive, but not poorly aggressive melanoma tumor cells express endothelial and epithelial markers and form vasculogenic-like networks similar to embryonic vasculogenesis. Vasculogenic mimicry is one example of the remarkable plasticity demonstrated by aggressive melanoma cells and suggests that these cells have acquired an embryonic-like phenotype. Since the initial discovery of tumor cell vasculogenic mimicry by our laboratory, we have been focusing on understanding the molecular mechanisms that regulate this process. This review will highlight recent findings identifying key signal transduction events that regulate melanoma vasculogenic mimicry and their similarity to the signal transduction events responsible for promoting embryonic vasculogenesis and angiogenesis. Specifically, this review will focus on the role of the Eph receptors and ligands in embryonic vasculogenesis, angiogenesis, and vasculogenic mimicry. Developmental Dynamics 236:3283-3296, 2007.

show abstract

Section: Focal Adhesion Kinase Signaling As a Mediator Of Melanoma Vmsupporting

confidence: 76%

Deciphering the signaling events that promote melanoma tumor cell vasculogenic mimicry and their link to embryonic vasculogenesis: Role of the Eph receptors

Hess

Margaryan

Seftor

et al. 2007

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…63 On the other hand, eprhin-A1 down-regulates FAK In human glioma U251 cells. 64 Our present and previous results demonstrate that FAK protein levels can be both down-regulated (by motility) and up-regulated (by exposure to TGF-␤) in intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 88%

Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

Walsh

Ampasala

Hatfield

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) regulates cell migration, proliferation, and apoptosis. FAK protein is reduced at the edge of migrating gut epithelial sheets in vitro, but it has not been characterized in restitutive gut mucosa in vivo. Here we show that FAK and activated phospho-FAK (FAK 397 ) immunoreactivity was lower in epithelial cells immediately adjacent to human gastric and colonic ulcers in vivo, but dramatically increased in epithelia near the ulcers, possibly reflecting stimulation by growth factors absent in vitro. Transforming growth factor (TGF)-␤, but not fibroblast growth factor, platelet-derived growth factor, or vascular endothelial growth factor, increased FAK levels in Caco-2 and IEC-6 cells. Epithelial immunoreactivity to TGF-␤ and phospho-Smad3 was also higher near the ulcers, varying in parallel with FAK. The TGF-␤ receptor antagonist SB431542 completely blocked TGF-␤-induced Smad2/3 and p38 activation in IEC-6 cells. SB431542 , the p38 antagonist SB203580 , and siRNA-mediated reduction of Smad2 and p38␣ prevented TGF-␤ stimulation of both FAK transcription and translation (as measured via a FAK promoter-luciferase construct). Survival and function of epithelial cells depends critically on interactions between the extracellular matrix and cell surface integrins. These interactions are mediated through focal adhesions, multicomponent juxtamembrane structures that lie at the convergence of integrin adhesion, signaling, and the cytoskeleton.1 Focal adhesion kinase (FAK) is an important nonreceptor tyrosine kinase within the focal adhesion complex.2 Originally described as being rapidly tyrosine phosphorylated on integrin-mediated cell-matrix adhesion, FAK is now known to be activated during epithelial cell motility and phosphorylated at both serine and tyrosine residues by various factors.3-5 Once localized to sites of transmembrane integrin receptor clustering, tyrosine-phosphorylated FAK plays a central role in signal transduction triggered by diverse extracellular signals 6 and represents a convergent point for synergistic interaction between signal pathways activated by growth factors and integrins.7 FAK binds to different signaling proteins via Src homology 2 (SH2) and SH3 recognition sites, acting as a scaffold and transmitting signals crucial to cell survival, motility, proliferation, and differentiation.8 FAK also regulates the cycle of focal contact formation and disassembly required for efficient cell movement and thus, mucosal restitution. 9Levels of FAK protein expression and/or activation have been correlated to phenotypic changes that affect cell differentiation and function, notably adhesion and migration, in a number of tissues. 10 -13 Targeted FAK deletion in vascular endothelial cells leads to apoptosis and aberrant cell movement whereas FAK overexpression results in increased angiogenesis.14,15 Total and activated FAK levels are also directly related to the state of differentiation in human colon cancer. 16 Induction of differentiation in dedifferentiated, rounded, detached Co...

show abstract

“…This receptor-ligand system is involved in a variety of biological events (Poliakov et al, 2004;Huberman et al, 2005;Kuijper et al, 2007). Although a majority of investigators have studied the role of Eph/ ephrin in development, emerging evidence suggests strong involvement in tumorigenesis, including metastasis, invasion, and angiogenesis (Surawska et al, 2004;BrantleySieders et al, 2006;Liu et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

et al. 2009

Oncogene

View full text Add to dashboard Cite

Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands play important roles in nervous system development. Recently, they have been implicated in tumorigenesis of different cancers. In this study, we showed that the expression of ephrinA5 was dramatically downregulated in primary gliomas compared with normal tissues. Forced expression of ephrinA5 reduced tumorigenicity of human glioma U373 cells. Epidermal growth factor receptor (EGFR), which frequently acts as an oncoprotein in glioma, was greatly decreased in ephrinA5-transfected glioma cells, and the two molecules exhibited a mutually exclusive expression pattern in primary glioma samples. We found that ephrinA5 enhanced c-Cbl binding to EGFR, thus promoted ubiquitylation and degradation of the receptor. Either ephrinA5-Fc or EphA2-Fc treatment simulating bidirectional signaling of Eph/ephrin system resulted in EGFR decrease. This study discovered that ephrinA5 acted as a tumor suppressor in glioma, and its negative regulation of EGFR contributed to the suppressive effects. In addition to identifying a novel mechanism underlying tumor suppressor activity of ephrinA5, we also showed cross-talk between different receptor tyrosine kinase families in glioma. These findings may improve therapeutic strategies for glioma.

show abstract

Ephrin-A1 is a negative regulator in glioma through down-reguation of EphA2 and FAK

Cited by 36 publications

References 28 publications

Deciphering the signaling events that promote melanoma tumor cell vasculogenic mimicry and their link to embryonic vasculogenesis: Role of the Eph receptors

Deciphering the signaling events that promote melanoma tumor cell vasculogenic mimicry and their link to embryonic vasculogenesis: Role of the Eph receptors

Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

Contact Info

Product

Resources

About