Nectin-4, a New Serological Breast Cancer Marker, Is a Substrate for Tumor Necrosis Factor-α-converting Enzyme (TACE)/ADAM-17

Fabre‐Lafay, Stéphanie; Garrido‐Urbani, Sarah; Reymond, Nicolas; Gonçalvès, Anthony; Dubreuil, Patrice; Lopez, Marc

doi:10.1074/jbc.m410943200

Cited by 140 publications

(105 citation statements)

References 43 publications

(19 reference statements)

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“…Ectodomain shedding essentially disrupts cell adhesion and supports cell movement (Arribas and Borroto, 2002). In terms of cell adhesion, E-and N-cadherin, ␥-protocadherin, nectin-1 and -4, and desmoglein-2 have all been shown to be cleaved specifically in their ectodomains by ADAM proteins (Kim et al, 2002;Fabre-Lafay et al, 2005;Haas et al, 2005;Maretzky et al, 2005;Reiss et al, 2005Reiss et al, , 2006BechSerra et al, 2006). Surprisingly, integrins only serve as ligands for ADAMs (Seals and Courtneidge, 2003;White, 2003); they have not been reported to be cleaved by members of the ADAM protein family.…”

Section: Cytokines and Growth Factorsmentioning

confidence: 99%

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

2008

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Section: Cytokines and Growth Factorsmentioning

confidence: 99%

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

2008

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“…In addition, several studies have shown that TACE expression is elevated under pathological conditions. In mammary tumor tissues, TACE protein levels are higher than in normal tissues (13,14). Also, elevated levels of TACE mRNA expression were found in osteoarthritis (15) and rheumatoid arthritis (RA)-affected cartilage as compared with normal cartilage (16), suggesting that abnormal TACE activity may contribute to the development of several pathological conditions, including RA.…”

mentioning

confidence: 99%

Hypoxia-inducible Factor Mediates Hypoxic and Tumor Necrosis Factor α-induced Increases in Tumor Necrosis Factor-α Converting Enzyme/ADAM17 Expression by Synovial Cells

Charbonneau¹,

Harper²,

Grondin³

et al. 2007

Journal of Biological Chemistry

104

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Chronic hypoxia and inflammatory cytokines are hallmarks of inflammatory joint diseases like rheumatoid arthritis (RA), suggesting a link between this microenvironment and central pathological events. Because TACE/ADAM17 is the predominant protease catalyzing the release of tumor necrosis factor ␣ (TNF␣), a cytokine that triggers a cascade of events leading to RA, we examined the regulation of this metalloprotease in response to hypoxia and TNF␣ itself. We report that low oxygen concentrations and TNF␣ enhance TACE mRNA levels in synovial cells through direct binding of hypoxia-inducible factor-1 (HIF-1) to the 5 promoter region. This is associated with elevated TACE activity as shown by the increase in TNF␣ shedding rate. By the use of HIF-1-deficient cells and by obliterating NF-B activation, it was determined that the hypoxic TACE response is mediated by HIF-1 signaling, whereas the regulation by TNF␣ also requires NF-B activation. As a support for the in vivo relevance of the HIF-1 axis for TACE regulation, immunohistological analysis of TACE and HIF-1 expression in RA synovium indicates that TACE is up-regulated in both fibroblast-and macrophage-like synovial cells where it localizes with elevated expression of both HIF-1 and TNF␣. These findings suggest a mechanism by which TACE is increased in RA-affected joints. They also provide novel mechanistic clues on the influence of the hypoxic and inflammatory microenvironment on joint diseases.Tumor necrosis factor-␣ converting enzyme (TACE) 2 or ADAM17 was initially described as the predominant enzyme responsible for the physiological cleavage of membrane-anchored tumor necrosis factor-␣ (TNF␣), releasing it in soluble form (1, 2). This enzyme belongs to the ADAM (a disintegrin and metalloprotease domain) family of transmembrane, multidomain zinc metalloproteinases (3) and is expressed in a wide variety of cell types, including TNF␣ non-producing cells (1). Beside TNF␣, TACE was also shown to solubilize a wide variety of proteins including the receptors TNFR-I and TNFR-II (4), interleukin-1RII (5), interleukin-6R (6), and macrophage/colony-stimulating factor-R (7), the cytokine transforming growth factor-␣ (4), members of the membrane-bound epidermal growth factor family (4), the Notch receptor (8), the chemokine fractalkine (9), L-selectin (4), and the ␤-amyloid precursor protein (10). The importance of TACE substrates in a variety of physiological functions, including development, is underscored by the fact that in vivo inhibition of TACE or disruption of the TACE gene results in the death of mice between embryonic day 17.5 and the first day after birth, due to a number of developmental defects. In addition, the implication of TACE substrates in immunoregulation has made this enzyme an efficient therapeutic target in the treatment of a number of pathological conditions including airway inflammation, cancer, and arthritis.Because of the pathophysiological importance of TACE-mediated shedding, several studies have addressed the mechanism of TACE regulation. Sur...

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“…TIGIT/WUCAM Introduction CD155 represents an Ig-like glycoprotein [1] and is the founder of a subfamily of adhesion receptors comprising also the related nectins 1-4. CD155/nectins take part in the complex regulation of cell growth, differentiation and motility [2,3], thereby in part explaining their identification as tumor markers [4][5][6][7]. Current evidence suggests that in contrast to nectins, CD155 acquired immunologically relevant functions.…”

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Abundance of follicular helper T cells in Peyer's patches is modulated by CD155

et al. 2009

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The secondary humoral immune response is characterized by plasma B cells secreting isotype-switched and affinity-matured antibodies. The efficient generation of plasma B cells in the GC depends on the presence of follicular helper T (T FH ) cells, a cell type thought to arise from naive CD4-positive T cells by a hitherto unresolved differentiation pathway. Mice deficient for CD155, an adhesion receptor of the immunoglobulin superfamily, are impaired to mount a secondary humoral immune response upon oral administration of antigen, while the primary IgM response is unaffected. Here, we show that mice lacking CD155 harbor significantly reduced numbers of T FH cells in their Peyer's patches. This was paralleled by a decreased frequency of T FH cells in the GC. Moreover, the CD155 ligand CD226, which is involved in T-cell activation, is down-regulated during T FH cell differentiation, resulting in a complete absence of CD226 on those T FH cells residing in the GC. Concurrently, the expression of TIGIT/WUCAM, a newly discovered CD155 ligand, is induced in T FH cells. Thus, these cells replace an activating by a putative inhibitory CD155-binding partner during their differentiation.Key words: CD155 . CD226 . Follicular helper T cells . GC . TIGIT/WUCAM Introduction CD155 represents an Ig-like glycoprotein [1] and is the founder of a subfamily of adhesion receptors comprising also the related nectins 1-4. CD155/nectins take part in the complex regulation of cell growth, differentiation and motility [2,3], thereby in part explaining their identification as tumor markers [4][5][6][7]. Current evidence suggests that in contrast to nectins, CD155 acquired immunologically relevant functions. This apparent, yet not absolute, functional dichotomy in the CD155 family may relate to the observation that CD155 belongs to the category of rapidly evolving genes [8] that may promote the occurrence of new receptor/ligand interactions. In contrast to nectins, CD155 lacks self-adhesion [8]. Instead, CD155 binds to nectin-3 [9], vitronectin [10], CD96 [11,12], CD226 [13] as well as the most recently discovered TIGIT/WUCAM [14,15]. CD155 is broadly expressed among immune cells [16], whereas the expression patterns of the activating receptor CD226 and the potentially inhibitory TIGIT/WUCAM are more restricted. In the T lineage, CD155 is present on T cells of virtually all stages of differentiation, ranging from early thymocytes to the antigen-experienced memory T cells [16]. CD226 is first observed on single positive thymocytes [17] and its subsequent expression is subject to regulation depending on the differentiation path following antigen challenge [18]. Inversely, TIGIT/WUCAM is absent from resting human PBMC and is only expressed upon stimulation [14,15]. Interestingly, immature DC up-regulate CD155 upon stimulation [16], suggesting a role of this receptor in T-cell priming. CD226 was assigned a co-stimulatory capacity [19][20][21] and its interaction with CD155 is pivotal in cytotoxic T/NKdirected lysis of targets such as immature DC...

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Nectin-4, a New Serological Breast Cancer Marker, Is a Substrate for Tumor Necrosis Factor-α-converting Enzyme (TACE)/ADAM-17

Cited by 140 publications

References 43 publications

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

Hypoxia-inducible Factor Mediates Hypoxic and Tumor Necrosis Factor α-induced Increases in Tumor Necrosis Factor-α Converting Enzyme/ADAM17 Expression by Synovial Cells

Abundance of follicular helper T cells in Peyer's patches is modulated by CD155

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