TNF-α-converting enzyme (TACE/ADAM17)-dependent loss of CD30 induced by proteasome inhibition through reactive oxygen species

Vahdat, A. M.; Reiners, Katrin S.; Simhadri, Vijaya L.; Eichenauer, Dennis A.; Böll, Boris; Chalaris, Athena; Wiegmann, Katja; Krell, Hans-Willi; Rose-John, Stefan; Engert, Andreas; Strandmann, Elke Pogge von; Hansen, Hinrich P.

doi:10.1038/leu.2009.230

Cited by 27 publications

(15 citation statements)

References 28 publications

(31 reference statements)

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“…These discrepancies may depend on the different cellular systems and/or experimental conditions used. Our evidence for ROS involvement in ADAM10 upregulation and MICB shedding are in line with the notion that conditions causing cellular stress, including ionizing radiation, chemotherapeutic agents, or ROS, can lead to increased metalloproteinase-mediated release of cell surface molecules (49)(50)(51) and suggest that stress stimuli promote the proteolytic process by upregulating metalloproteinase expression and activity. We also are the first to describe, to our knowledge, that genotoxic stress-induced upregulation of ADAM10 expression and sMICB secretion are primarily associated with senescent cells.…”

Section: Discussionsupporting

confidence: 70%

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Zingoni

Cecere

Vulpis

et al. 2015

The Journal of Immunology

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Genotoxic stress can promote antitumor NK cell responses by upregulating the surface expression of activating ligands on cancer cells. Moreover, a number of studies suggested a role for soluble NK group 2D ligands in the impairment of NK cell tumor recognition and killing. We investigated whether genotoxic stress could promote the release of NK group 2D ligands (MHC class I-related chain [MIC]A and MICB), as well as the molecular mechanisms underlying this event in human multiple myeloma (MM) cells. Our results show that genotoxic agents used in the therapy of MM (i.e., doxorubicin and melphalan) selectively affect the shedding of MIC molecules that are sensitive to proteolytic cleavage, whereas the release of the short MICA*008 allele, which is frequent in the white population, is not perturbed. In addition, we found that a disintegrin and metalloproteinase 10 expression is upregulated upon chemotherapeutic treatment both in patient-derived CD138(+)/CD38(+) plasma cells and in several MM cell lines, and we demonstrate a crucial role for this sheddase in the proteolytic cleavage of MIC by means of silencing and pharmacological inhibition. Interestingly, the drug-induced upregulation of a disintegrin and metalloproteinase 10 on MM cells is associated with a senescent phenotype and requires generation of reactive oxygen species. Moreover, the combined use of chemotherapeutic drugs and metalloproteinase inhibitors enhances NK cell-mediated recognition of MM cells, preserving MIC molecules on the cell surface and suggesting that targeting of metalloproteinases in conjunction with chemotherapy could be exploited for NK cell-based immunotherapeutic approaches, thus contributing to avoid the escape of malignant cells from stress-elicited immune responses

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Section: Discussionsupporting

confidence: 70%

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Zingoni

Cecere

Vulpis

et al. 2015

The Journal of Immunology

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“…Although blocking ADAM17 could simultaneously shut down multiple pathogenic pathways and has been proposed for treating chronic kidney diseases not related to LN (15)(16)(17), there are substantial concerns about therapeutically targeting ADAM17, mainly because ADAM17 has an essential role in protecting the skin and intestinal barrier through activating the EGFR pathway (18,19). Indeed, mice lacking Adam17 die at birth due to defects in EGFR signaling, and individuals with ADAM17 mutation or those treated with EGFR inhibitors display skin and intestinal inflammation (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling

Qing¹,

Chinenov²,

Redecha³

et al. 2018

Journal of Clinical Investigation

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“…In addition, the proteasomal inhibitor MG132 increased not only HIF1a and ATF4, but also ADAM17 levels (data not shown). In support, the proteasome inhibitor bortezomib increased ADAM17 shedding activity (Vahdat et al, 2010). Thus, one might speculate that under conditions associated with proteasomal inhibition, ADAM17 levels and processing may be increased.…”

Section: Discussionmentioning

confidence: 99%

The unfolded protein response controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress

et al. 2011

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The family of ADAM (a disintegrin and metalloproteinase) proteins has been implicated in tumor initiation and progression. ADAM17/tumor necrosis factor-a (TNFa)-converting enzyme (TACE) has been initially recognized to release TNFa as well as its receptors (TNFRs) from the membrane. ADAM17, TNFa and TNFR have been found upregulated in cancer patients, although the underlying mechanisms remain largely unknown. As hypoxia is a hallmark of cancer that can lead to severe stress conditions accumulating in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), we investigated the role of these stress conditions in the regulation of ADAM17 and release of TNFR1.We found that severe hypoxia induced ADAM17 expression and activity. Although hypoxia-inducible factor 1a (HIF1a) was important to maintain basal ADAM17 mRNA levels during moderate hypoxia, it was not sufficient to induce ADAM17 levels under severe hypoxia. Instead, we found that ADAM17 induction by severe hypoxia can be mimicked by ER stressors such as Thapsigargin and occurs as a consequence of the activation of the PERK/eIF2a/ATF4 and activating transcription factor 6 (ATF6) arms of UPR in several tumor cell lines. ADAM17 expression was also increased in xenografts displaying ER stress because of treatment with the vascular endothelial growth factor (VEGF) inhibitory antibody Bevacizumab. Additionally, severe hypoxia and ER stress activated ADAM17 and ectodomain shedding of TNFR1 involving mitogen-activated protein (MAP) kinases and reactive oxygen species (ROS). Collectively, these results show that ADAM17 is a novel UPRregulated gene in response to severe hypoxia and ER stress, which is actively involved in the release of TNFR1 under these conditions. These data provide a novel link between severe hypoxic stress conditions and inflammation in the tumor environment.

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TNF-α-converting enzyme (TACE/ADAM17)-dependent loss of CD30 induced by proteasome inhibition through reactive oxygen species

Cited by 27 publications

References 28 publications

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling

The unfolded protein response controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress

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