In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Jiang, Guangping; Freywald, Tanya; Webster, Jarret; Kozan, Daniel; Geyer, Ron; DeCoteau, John F.; Narendran, Aru; Freywald, Andrew

doi:10.1158/1541-7786.mcr-07-0047

Cited by 20 publications

(21 citation statements)

References 93 publications

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“…Extracellular EphA2 cleavage by the membrane-anchored, membrane type-1 matrix metalloproteinase (MT1-MMP) has been implicated in the disassembly of cell-cell contacts and cancer cell invasion (Sugiyama et al 2013). Further, ephrinB1 reverse signaling can promote tumor cell invasion by inducing MMP8 secretion (Tanaka et al 2007a,b;Jiang et al 2008). These findings suggest a central role for Eph/ephrin in the progression of epithelial cells toward a metastatic state by regulating cell-cell and cell-matrix adhesion.…”

Section: Eph-ephrin Regulation Of Adherens Junctionsmentioning

confidence: 99%

Making Connections: Guidance Cues and Receptors at Nonneural Cell–Cell Junctions

Beamish

Hinck

Kennedy

2017

Cold Spring Harb Perspect Biol

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The field of axon guidance was revolutionized over the past three decades by the identification of highly conserved families of guidance cues and receptors. These proteins are essential for normal neural development and function, directing cell and axon migration, neuron-glial interactions, and synapse formation and plasticity. Many of these genes are also expressed outside the nervous system in which they influence cell migration, adhesion and proliferation. Because the nervous system develops from neural epithelium, it is perhaps not surprising that these guidance cues have significant nonneural roles in governing the specialized junctional connections between cells in polarized epithelia. The following review addresses roles for ephrins, semaphorins, netrins, slits and their receptors in regulating adherens, tight, and gap junctions in nonneural epithelia and endothelia.

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Section: Eph-ephrin Regulation Of Adherens Junctionsmentioning

confidence: 99%

Making Connections: Guidance Cues and Receptors at Nonneural Cell–Cell Junctions

Beamish

Hinck

Kennedy

2017

Cold Spring Harb Perspect Biol

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“…The first-strand cDNA was obtained and PCR was performed as previously described (51). The PCR primers for EphB2, EphB3, EphB4, EphB6, and b-actin were described previously (51,60,61) and synthesized by Sigma-Genosys (Oakville, ON, Canada). EphB1 (59-CAAGACTGTGGCAACCATCAC-CG-39, and 59-GTGACTGACTTATCTGGACCCTC-39) and EphA4 (59-CTGCTGGCAGAAGGAGAGGAGC-39, and 59-CTGGTGCGTGATGG-CTGTGATAC-39) primers were also synthesized by Sigma-Genosys.…”

Section: Rt-pcr Assaymentioning

confidence: 99%

“…All analyses represent one of at least two independent experiments. lymphoid malignancies, predominantly through the regulation of attachment and invasive properties of leukemic cells (47,(51)(52)(53). Meanwhile, little is known about the potential involvement of the ephrin-B-interacting Ephs, EphB1-4, EphB6, and EphA4 (34), collectively referred to as EphrinB receptors.…”

Section: Ephb Receptors Are Expressed By Malignant T Cells and Protecmentioning

confidence: 99%

“…It has been reported that some Eph receptors and ephrin genes have their promoter regions methylated in leukemic cells, and that overexpressed EphB4 inhibits Akt activation, thus inducing apoptotic cell death in Raji B-ALL cells (44). Nevertheless, expression of some Ephs and ephrins, including EphA1, EphA2, EphA3, EphA7, EpA10, EphB6, ephrin-A4, ephrin-B1, and ephrin-B2, has been observed in ALL cell lines and chronic lymphocytic leukemia patient samples (45)(46)(47)(48)(49)(50)(51). Moreover, ephrin-A4, EphA3, and ephrin-B1 are actively involved in the regulation of cell attachment and invasive properties in chronic lymphocytic leukemia, B cell ALL, and T-ALL cells (47,(51)(52)(53).…”

mentioning

confidence: 99%

“…Nevertheless, expression of some Ephs and ephrins, including EphA1, EphA2, EphA3, EphA7, EpA10, EphB6, ephrin-A4, ephrin-B1, and ephrin-B2, has been observed in ALL cell lines and chronic lymphocytic leukemia patient samples (45)(46)(47)(48)(49)(50)(51). Moreover, ephrin-A4, EphA3, and ephrin-B1 are actively involved in the regulation of cell attachment and invasive properties in chronic lymphocytic leukemia, B cell ALL, and T-ALL cells (47,(51)(52)(53). Complementing each other, these observations suggest that a disbalance in Eph receptor signaling caused by distorted expression patterns, rather than its complete blockage, is likely to contribute toward the malignant behavior of leukemic cells.…”

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confidence: 99%

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EphB Receptors Trigger Akt Activation and Suppress Fas Receptor-Induced Apoptosis in Malignant T Lymphocytes

Maddigan

Truitt

Arsenault

et al. 2011

The Journal of Immunology

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Treatment of hematopoietic malignancies often requires allogeneic bone marrow transplantation, and the subsequent graft-versus-leukemia response is crucial for the elimination of malignant cells. Cytotoxic T lymphocytes and NK cells responsible for the immunoelimination express Fas ligand and strongly rely on the induction of Fas receptor-mediated apoptosis for their action. Although cancer cells are removed successfully by graft-versus-leukemia reactions in myeloid malignancies, their efficiency is low in T cell leukemias. This may be partially because of the ability of malignant T cells to escape apoptosis. Our work shows that Eph family receptor EphB3 is consistently expressed by malignant T lymphocytes, most frequently in combination with EphB6, and that stimulation with their common ligands, ephrin-B1 and ephrin-B2, strongly suppresses Fas-induced apoptosis in these cells. This effect is associated with Akt activation and with the inhibition of the Fas receptor-initiated caspase proteolytic cascade. Akt proved to be crucial for the prosurvival response, because inhibition of Akt, but not of other molecules central to T cell biology, including Src kinases, MEK1 and MEK2, blocked the antiapoptotic effect. Overall, this demonstrates a new role for EphB receptors in the protection of malignant T cells from Fas-induced apoptosis through Akt engagement and prevention of caspase activation. Because Fas-triggered apoptosis is actively involved in the graft-versus-leukemia response and cytotoxic T cells express ephrin-Bs, our observations suggest that EphB receptors are likely to support immunoevasivenes of T cell malignancies and may represent promising targets for therapies, aiming to enhance immunoelimination of cancerous T cells.

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Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stage

Baruthio¹,

Quadroni

Rüegg³

et al. 2008

Proteomics

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The molecular mechanisms controlling the progression of melanoma from a localized tumor to an invasive and metastatic disease are poorly understood. In the attempt to start defining a functional protein profile of melanoma progression, we have analyzed by LC-MS/MS the proteins associated with detergent resistant membranes (DRMs), which are enriched in cholesterol/sphingolipids-containing membrane rafts, of melanoma cell lines derived from tumors at different stages of progression. Since membrane rafts are involved in several biological processes, including signal transduction and protein trafficking, we hypothesized that the association of proteins with rafts can be regulated during melanoma development and affect protein function and disease progression. We have identified a total of 177 proteins in the DRMs of the cell lines examined. Among these, we have found groups of proteins preferentially associated with DRMs of either less malignant radial growth phase/vertical growth phase (VGP) cells, or aggressive VGP and metastatic cells suggesting that melanoma cells with different degrees of malignancy have different DRM profiles. Moreover, some proteins were found in DRMs of only some cell lines despite being expressed at similar levels in all the cell lines examined, suggesting the existence of mechanisms controlling their association with DRMs. We expect that understanding the mechanisms regulating DRM targeting and the activity of the proteins differentially associated with DRMs in relation to cell malignancy will help identify new molecular determinants of melanoma progression.

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In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Cited by 20 publications

References 93 publications

Making Connections: Guidance Cues and Receptors at Nonneural Cell–Cell Junctions

Making Connections: Guidance Cues and Receptors at Nonneural Cell–Cell Junctions

EphB Receptors Trigger Akt Activation and Suppress Fas Receptor-Induced Apoptosis in Malignant T Lymphocytes

Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stage

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