Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling

Natoli, Gioacchino; Costanzo, Antonio; Guido, Francesco; Moretti, Francesca; Levrero, Massimo

doi:10.1016/s0006-2952(98)00154-3

Cited by 129 publications

(79 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While our results point toward the role of GCK in the ability of TRAF2 to dictate the susceptibility to UV-induced apoptosis, the contribution of other components of TRAF-dependent signaling, including RIP, NIK and Siah1a (Yuasa et al, 1998;Song et al, 1997;Ting et al, 1996), as well as other TRAF family members is yet to be determined. The nature of TRAF2/GCK e ectors may explain the diverse (anti/pro) apoptotic signaling attributed to TNF/TRAF2 (reviewed in Natoli et al, 1998b), and which was also observed in the current study.…”

Section: Discussionsupporting

confidence: 74%

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

2000

View full text Add to dashboard Cite

Radiation resistance is a hallmark of human melanoma, and yet mechanisms underlying this resistance are not well understood. We recently established the role of ATF2 in this process, suggesting that stress kinases, which contribute to regulation of ATF2 stability and activity, play an important role in the acquisition of such resistance. Here we demonstrate that changes in the expression and respective activities of TRAF2/GCK occur during melanoma development and regulate its sensitivity to UV-induced apoptosis. Comparing earlyand late-stage melanoma cells revealed low expression of TRAF2 and GCK in early-stage melanoma, which coincided with poor resistance to UV-induced, TNFmediated apoptosis; forced expression of GCK alone or in combination with TRAF2 e ciently increased JNK and NF-kB activities, which coincided with increased protection against apoptosis. Conversely, forced expression of the dominant negative form of TRAF2 or GCK in late-stage melanoma cells reduced NF-kB activity and decreased Fas expression, resulting in a lower degree of UV-induced, Fas-mediated cell death. Our results illustrate a mechanism in which protection from, or promotion of, UV-induced melanoma cell death depends on the nature of the apoptotic cascade (TNF or Fas) and on the availability of TRAF2/GCK, whose expression increases during melanoma progression. Oncogene (2000) 19, 933 ± 942.

show abstract

Section: Discussionsupporting

confidence: 74%

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

2000

View full text Add to dashboard Cite

show abstract

“…A variety of receptors have been shown to cluster upon stimulation: the TCR-CD3 complex (1,2), B cell receptor (BCR) 3 (3,4), CD40 (5,6), Fc⑀RI (7), CD95 (8 -10), CD28 (11), TNFR (12), platelet-derived growth factor receptor (13), CD2, CD44, L-selectin, or integrins (14). Many receptor molecules cluster in distinct cholesterol-and sphingolipidrich domains of the cell membrane termed rafts (15)(16)(17).…”

mentioning

confidence: 99%

Ceramide-Rich Membrane Rafts Mediate CD40 Clustering

Grassmé

Jendrossek

Bock

et al. 2002

The Journal of Immunology

241

211

View full text Add to dashboard Cite

Many receptor systems use receptor clustering for transmembrane signaling. In this study, we show that acid sphingomyelinase (ASM) is essential for the clustering of CD40. Stimulation of lymphocytes via CD40 ligation results in ASM translocation from intracellular stores, most likely vesicles, into distinct membrane domains on the extracellular surface of the plasma membrane. Surface ASM initiates a release of extracellularly oriented ceramide, which in turn mediates CD40 clustering in sphingolipid-rich membrane domains. ASM, ceramide, and CD40 colocalize in the cap-like structure of stimulated cells. Deficiency of ASM, destruction of sphingolipid-rich rafts, or neutralization of surface ceramide prevents CD40 clustering and CD40-initiated cell signaling. These findings indicate that the ASM-mediated release of ceramide and/or metabolites of ceramide regulate clustering of CD40, which seems to be a prerequisite for cellular activation via CD40.

show abstract

“…In many non-transformed cells, however, TNF is thought to mediate an important prosurvival role. For example, cell death in response to TNF is rarely observed in normal cells unless inhibitors of transcription or translation are concurrently administered, suggesting gene regulatory pathways regulated by TNF signaling include cytoprotective pathways (2,3). In particular, normal mammary epithelial cells (MECs) are relatively resistant to TNF cytotoxicity as compared with mammary cancer cells (4,5), and some reports suggest TNF plays a physiological role as both a survival factor and mitogen in normal mammary epithelium (6 -8).…”

mentioning

confidence: 99%

Induced Autocrine Signaling through the Epidermal Growth Factor Receptor Contributes to the Response of Mammary Epithelial Cells to Tumor Necrosis Factor α

Chen

Woodbury

Kathmann

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

In contrast to the well known cytotoxic effects of tumor necrosis factor (TNF) ␣ in many mammary cancer cells, we have found that TNF stimulates the proliferation and motility of human mammary epithelial cells (HMECs). Since the response of HMECs to TNF is similar to effects mediated by epidermal growth factor receptor (EGFR) activation, we explored the potential role of cross-talk through the EGFR signaling pathways in mediating cellular responses to TNF. Using a microarray enzyme-linked immunoassay, we found that exposure to TNF stimulated the dose-dependent shedding of the EGFR ligand transforming growth factor ␣ (TGF␣). Both proliferation and motility of HMECs induced by TNF was prevented either by inhibiting membrane protein shedding with a metalloprotease inhibitor, by blocking epidermal growth factor receptor (EGFR) kinase activity, or by limiting ligand-receptor interactions with an antagonistic anti-EGFR antibody. EGFR activity was also necessary for TNF-induced release of matrix metalloprotease-9, thought to be an essential regulator of mammary cell migration. The cellular response to TNF was associated with a biphasic temporal pattern of extracellular signal-regulated kinase (ERK) phosphorylation, which was EGFR-dependent and modulated by inhibition of metalloprotease-mediated shedding. Significantly, the late phase of ERK phosphorylation, detectable within 4 h after exposure, was blocked by the metalloprotease inhibitor batimastat, indicating that autocrine signaling through ligand shedding was responsible for this secondary wave of ERK activity. Our results indicate a novel and important role for metalloprotease activation and EGFR transmodulation in mediating the cellular response to TNF. Tumor necrosis factor (TNF)1 ␣ is a potent cytokine produced by many cell types in response to inflammation, infection, and environmental stress. Originally discovered for its ability to induce hemorrhagic necrosis in tumor cells (1), TNF is perhaps best known for inducing cytotoxicity and apoptosis in transformed cells. In many non-transformed cells, however, TNF is thought to mediate an important prosurvival role. For example, cell death in response to TNF is rarely observed in normal cells unless inhibitors of transcription or translation are concurrently administered, suggesting gene regulatory pathways regulated by TNF signaling include cytoprotective pathways (2, 3). In particular, normal mammary epithelial cells (MECs) are relatively resistant to TNF cytotoxicity as compared with mammary cancer cells (4, 5), and some reports suggest TNF plays a physiological role as both a survival factor and mitogen in normal mammary epithelium (6 -8). For example, in primary rat MECs, TNF stimulates proliferation and up-regulates matrix metalloproteases necessary for cell motility and branching morphogenesis (6, 7). MEC proliferation and branching during puberty is also delayed in TNF null mice (9). Consistent with having an important physiological role, expression of TNF and its receptors is tightly regulated throughout ...

show abstract

Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling

Cited by 129 publications

References 47 publications

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

Ceramide-Rich Membrane Rafts Mediate CD40 Clustering

Induced Autocrine Signaling through the Epidermal Growth Factor Receptor Contributes to the Response of Mammary Epithelial Cells to Tumor Necrosis Factor α

Contact Info

Product

Resources

About