VEGI, a new member of the TNF family activates Nuclear Factor-κB and c-Jun N-terminal kinase and modulates cell growth

Haridas, Valsala; Shrivastava, Anju; Su, Jeffrey; Yu, Guo Liang; Ni, Jian; Liu, Ding; Chen, Su Fang; Ni, Yansong; Ruben, Steve; Gentz, Reiner; Aggarwal, Bharat B.

doi:10.1038/sj.onc.1203059

Cited by 64 publications

(40 citation statements)

References 37 publications

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“…VEGI is able to inhibit the growth of various human tumour cell lines including human histiocytic lymphoma (U-937), human breast carcinoma (MCF-7), human epithelial carcinoma (HeLa) and human myeloid lymphoma ML-1a (11). VEGI was also shown to inhibit tumour growth in vivo.…”

Section: Implication Of Vegi In Solid Tumoursmentioning

confidence: 99%

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Vascular endothelial growth inhibitor in human cancer (Review)

Zhang

Sanders²,

Ye³

et al. 2009

Int J Mol Med

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Abstract. Vascular endothelial growth inhibitor (VEGI), also known as tumour necrosis factor superfamily member 15 (TNFSF15) and TNF ligand related molecule 1 (TL1), is a recently identified anti-angiogenic cytokine that belongs to the TNF superfamily. Three isoforms of VEGI, VEGI 174, 192, and 251 have been documented, all sharing 151 common C-terminal amino acids but differing in their N-terminal regions. The investigations into the biological functions of VEGI have pointed to a potential cancer inhibitory role for the cytokine. The inhibitory effects of VEGI on cancer are manifested in three main areas, the direct effect on cancer cells, the anti-angiogenic effects on endothelial cells, and stimulation of maturation of dendric cells. The clinical aspect of VEGI in cancer is also being explored in recent years. The present article overviews the recent progress on this molecule and discusses the value of VEGI as a potential therapeutic target in cancer therapy. Contents1. Introduction 2. VEGI and TNF superfamily 3. Structure of VEGI and VEGI isoforms 4. Expression and cell/tissue distribution of VEGI 5. Regulation of VEGI expression 6. VEGI and angiogenesis 7. Implication of VEGI in solid tumours 8. Other functions of VEGI involved in carcinoma 9. Perspective IntroductionVascular endothelial growth inhibitor (VEGI) was first reported in 1999 from human umbilical vein endothelial cells (1,2) and was found to be identical to another gene known as tumour necrosis factor superfamily member 15 (TNFSF15) and TNF ligand related molecule 1 (TL1). The prime function of VEGI was thought to be anti-angiogenic (1,2). Originally, it was reported to be expressed exclusively in endothelial cells, but more recently VEGI 251 was found to be highly expressed in dendritic cells (DCs) after in vitro activation and in inflammatory bowel disease (IBD), particularly Crohn's disease (CD), rheumatoid arthritis, as well as renal inflammation (3-6). It was believed to be one of the evolutionarily earliest members of the TNF superfamily (7). There is evidence showing that VEGI is involved in atherogenesis. Thus, VEGI is a multipotential cytokine and plays a role in inflammation, septic shock, fever, and growth modulation through the functions of inducing apoptosis, regulating immunity, and anti-angiogenesis.Moreover, other studies demonstrated an intricate relationship between VEGI and carcinoma in vitro and in vivo (8-11). It is a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumour growth (12). The present review will briefly discuss the VEGI family and focus on the impact of VEGI in cancer. VEGI and the TNF superfamilyThree decades ago, lymphotoxin (LT) and tumour necrosis factor-· (TNF) were identified as products of lymphocytes and macrophages that cause lysis of certain types of cells, especially tumour cells (13,14). The two molecules are members of a gene superfamily (15,16). There are at least 19 members so far identified within this family (Table I), which is generally referred to as tumour necrosis fact...

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Section: Implication Of Vegi In Solid Tumoursmentioning

confidence: 99%

“…Moreover, other studies demonstrated an intricate relationship between VEGI and carcinoma in vitro and in vivo (8)(9)(10)(11). It is a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumour growth (12).…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth inhibitor in human cancer (Review)

Zhang

Sanders²,

Ye³

et al. 2009

Int J Mol Med

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“…Many other members of the TNF superfamily also induce apoptosis. These include LT (lymphotoxin), FasL (fibroblast-associated ligand), TRAIL (TNF-related apoptosis-inducing ligand), DR3L (for death receptor 3 ligand or also known as TWEAK for a weak homologue of TNF), THANK (TNF homologue that activates apoptosis, NF-κB and JNK), and VEGI (vascular endothelial cell growth inhibitor) (Haridas et al, 1999;Mukhopadhyay et al, 1999). Whether all these TNF family members induce apoptosis by the same mechanism as TNF is unknown.…”

Section: Mechanism Of Apoptosismentioning

confidence: 99%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

205

168

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Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-κB activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-κB and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which may or may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-κB controls apoptosis.

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“…Overall, early evidence has indicated that the anti-tumour activity of VEGI is more likely to be the result of an interference with the development of tumourassociated vasculature rather than that of a direct effect on tumour cells (10,11,13,22). However, it has also been suggested that VEGI may inhibit the growth of human tumour cell lines, including human histiocytic lymphomas (U-937), human breast carcinomas (MCF-7), human epithelial carcinoma (HeLa) and human myeloid lymphomas ML-1a (23). So far, there is little work on the significance of VEGI in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth inhibitor, expression in human prostate cancer tissue and the impact on adhesion and migration of prostate cancer cells in vitro

Jiang¹

2009

Int J Oncol

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Abstract. Vascular endothelial growth inhibitor (VEGI) has been associated with tumour-related vasculature in certain maligancies. However, its implication in prostate cancer remains unknown. We investigated the expression pattern and role of VEGI in prostate cancer and prostate cancer cells. The expression of VEGI was examined in human prostate tissue and prostate cancer cell lines. The biological impact of modifying the expression of VEGI in prostate cancer cells was evaluated using in vitro models. VEGI mRNA was expressed in a wide variety of human prostate cancer cell lines and most prostate specimens. VEGI protein was seen in normal prostate epithelium, but was decreased or absent in prostate cancer specimens, particularly in tumours with high Gleason scores. Moreover, forced-expression of VEGI led to a decrease in the motility and adhesion of prostate cancer cells in vitro. In contrast, knocking down VEGI in the cells resulted in an increase in motility and adhesion. Interestingly, both forced-expression and knocking down of VEGI had no bearing on growth and invasive capacity of prostate cells. In conclusion, the expression of VEGI is decreased in prostate cancer and is almost absent in tumours with high Gleason scores. Together with its inhibitory effect on cellular motility and adhesion, this suggests that VEGI functions as a negative regulator for aggressiveness during the development and progression of prostate cancer.

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VEGI, a new member of the TNF family activates Nuclear Factor-κB and c-Jun N-terminal kinase and modulates cell growth

Cited by 64 publications

References 37 publications

Vascular endothelial growth inhibitor in human cancer (Review)

Vascular endothelial growth inhibitor in human cancer (Review)

Nuclear Factor-κB Activation: A Question of Life or Death

Vascular endothelial growth inhibitor, expression in human prostate cancer tissue and the impact on adhesion and migration of prostate cancer cells in vitro

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