TWEAK Induces Angiogenesis and Proliferation of Endothelial Cells

Lynch, Carolyn N.; Wang, Yi Chun; Lund, Jennifer K.; Chen, Yung-Wu; Leal, Juan; Wiley, Steven R.

doi:10.1074/jbc.274.13.8455

Cited by 228 publications

(213 citation statements)

References 38 publications

(25 reference statements)

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“…TWEAK, a member of the TNF family, induces cell death in some tumor cell lines (3,4), but also induces proliferation of human endothelial cells in vitro and angiogenesis in vivo (5). We have recently reported that TWEAK is expressed on IFN-␥-stimulated human monocytes and is involved in their cytotoxicity (6).…”

Section: Embers Of the Tnf Family Play Important Roles In Reg-mentioning

confidence: 99%

Fibroblast Growth Factor-Inducible 14 Mediates Multiple Pathways of TWEAK-Induced Cell Death

Nakayama¹,

Ishidoh²,

Kojima³

et al. 2003

The Journal of Immunology

132

133

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TWEAK, a TNF family member, is produced by IFN-γ-stimulated monocytes and induces multiple pathways of cell death, including caspase-dependent apoptosis, cathepsin B-dependent necrosis, and endogenous TNF-α-mediated cell death, in a cell type-specific manner. However, the TWEAK receptor(s) that mediates these multiple death pathways remains to be identified. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which was responsible for TWEAK-induced proliferation of endothelial cells and angiogenesis. Because Fn14 lacks the cytoplasmic death domain, it remains unclear whether Fn14 can also mediate the TWEAK-induced cell death. In this study, we demonstrated that TWEAK could induce apoptotic cell death in Fn14 transfectants. A pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, rather sensitized the Fn14 transfectants to TWEAK-induced cell death by necrosis via reactive oxygen intermediates and cathepsin B-dependent pathway. By using newly generated agonistic anti-Fn14 mAbs, we also observed that Fn14 is constitutively expressed on the cell surface of all TWEAK-sensitive tumor cell lines, and can transmit the multiple death signals. Moreover, an anti-Fn14 mAb that blocks TWEAK-Fn14 interaction could totally abrogate TWEAK binding and TWEAK-induced cell death in all TWEAK-sensitive tumor cell lines. These results revealed that the multiple pathways of TWEAK-induced cell death are solely mediated by Fn14.

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Section: Embers Of the Tnf Family Play Important Roles In Reg-mentioning

confidence: 99%

Fibroblast Growth Factor-Inducible 14 Mediates Multiple Pathways of TWEAK-Induced Cell Death

Nakayama¹,

Ishidoh²,

Kojima³

et al. 2003

The Journal of Immunology

132

133

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“…Unlike TRAIL, TWEAK induces cell proliferation and not apoptosis when added to astrocytes (5,6,8,43). Here we investigated the effect of TWEAK on glioma cell survival.…”

Section: Tweak Protects Glioma Cells From Cytotoxic Therapy-induced Amentioning

confidence: 99%

“…In both endothelial cells and astrocytes, TWEAK promotes cell proliferation and not death (5)(6)(7). TWEAK can also stimulate angiogenesis in vivo (8).…”

mentioning

confidence: 99%

The Tumor Necrosis Factor-like Weak Inducer of Apoptosis (TWEAK)-Fibroblast Growth Factor-inducible 14 (Fn14) Signaling System Regulates Glioma Cell Survival via NFκB Pathway Activation and BCL-XL/BCL-W Expression

Tran

McDonough

Savitch

et al. 2005

Journal of Biological Chemistry

169

177

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“…The potential biological role of TWEAK and FN14 in the wound response of normal tissues was initially supported by several studies demonstrating that TWEAK is angiogenic 1,11,12 and that FN14 expression is elevated in the proliferating endothelial and smooth muscle cells of damaged rat arteries. 1 More recently it has been shown that TWEAK can associate with another novel secreted angiogenic factor, VG5Q, which is mutated in the vascular disease KlippelTrenaunay syndrome, 13 but, the biological significance of this interaction has yet to be elucidated.…”

mentioning

confidence: 98%

TWEAK shall inherit the earth

Vince

Silke

2006

Cell Death Differ

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Sometimes size really does not matter: recent papers on the tumour necrosis factor (TNF)-like ligand, TWEAK (tumour necrosis factor-like weak inducer of apoptosis), and its diminutive 129 amino-acid receptor, FN14 (fibroblast growth factor (FGF) -inducible 14 kDa protein), describe an impressive and potent range of biological effects. The TNF superfamily (TNSF) receptor FN14 has a small cytoplasmic domain, and the limited similarity of its extracellular domain to the cysteine-rich domains of the TNFSF receptors was only appreciated retrospectively when it was discovered that it bound TWEAK. 1 Recent work has demonstrated that TWEAK knockout animals have an activated immune system that is skewed by elevated numbers of natural killer (NK) cells and responds lethally to bacterial endotoxins, but also shows a powerful ability to prevent tumour growth. 2 Other topical papers show that TWEAK and FN14 work to promote liver regeneration following injury and prevent the differentiation of a diverse range of cell types. The role of TWEAK and FN14 in cancer has yet to be conclusively established, but several groups have observed high expression of FN14 in cancerous tissues, and demonstrated that it can promote cellular functions important for tumorigenesis, including cytokine production, cellular proliferation, survival, migration and angiogenesis. 3 TWEAK is a type II transmembrane protein (extracellular C-terminus) that can undergo proteolysis to produce an active soluble homotrimer, 4,5 whereas FN14 is a type Ia transmembrane protein. 6 In some respects the potent effects of the ligand TWEAK are reminiscent to those of TNFa: both factors appear to play roles in inflammation, and both have the capacity to induce cell death, although usually in conjunction with another stimulus. Responses to TNFSF ligands can be complex because several ligands often bind to the same receptor and vice versa. For example, both the human ligands TNFa and LTa bind the receptors TNFR1 and TNFR2, whereas LTa also binds HVEM. In fact, more than half of the TNSF ligands bind to at least two receptors. 7 One of the amazing things about the TWEAK/FN14 system is that it is a simple, single ligand, single receptor system 7 in which the intracellular signalling domain of FN14 is only 28 amino acids. It remains possible that another TWEAK receptor exists 8 which might help to explain the diverse range of effects that TWEAK produces, but this is yet to be conclusively established.

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TWEAK Induces Angiogenesis and Proliferation of Endothelial Cells

Cited by 228 publications

References 38 publications

Fibroblast Growth Factor-Inducible 14 Mediates Multiple Pathways of TWEAK-Induced Cell Death

Fibroblast Growth Factor-Inducible 14 Mediates Multiple Pathways of TWEAK-Induced Cell Death

The Tumor Necrosis Factor-like Weak Inducer of Apoptosis (TWEAK)-Fibroblast Growth Factor-inducible 14 (Fn14) Signaling System Regulates Glioma Cell Survival via NFκB Pathway Activation and BCL-XL/BCL-W Expression

TWEAK shall inherit the earth

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