Selective Roles for Tumor Necrosis Factor α-converting Enzyme/ADAM17 in the Shedding of the Epidermal Growth Factor Receptor Ligand Family

Hinkle, C. Leann; Sunnarborg, Susan W.; Loiselle, David R.; Parker, Carol E.; Stevenson, Mary C.; Russell, William E.; Lee, Dong Hoon

doi:10.1074/jbc.m312141200

Cited by 133 publications

(113 citation statements)

References 81 publications

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“…Extensive data show that various members of the ADAM (a disintegrin and metalloproteinase) family of zinc-dependent cell surface enzymes that includes ADAM17 (TNFα converting enzyme, TACE), are responsible for the release of all EGFR ligands, including AREG, in culture [34][35][36][37]. Moreover, even juxtacrine activation of EGFR via direct cell-to-cell contact may require the ADAM17-mediated processing of EGFR agonists [38], although such contactdependent activation is almost certainly irrelevant during mammary development, since epithelial and stromal cells are generally separated by a basement membrane.…”

Section: Epithelial Adam17 Is Required For Mammary Developmentmentioning

confidence: 99%

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

Sternlicht

Sunnarborg

2008

J Mammary Gland Biol Neoplasia

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In order to fulfill its function of producing and delivering sufficient milk to newborn mammalian offspring, the mammary gland first has to form an extensive ductal network. As in all phases of mammary development, hormonal cues elicit local intra-and inter-cellular signaling cascades that regulate ductal growth and differentiation. Among other things, ductal development requires the epidermal growth factor receptor (EGFR), its ligand amphiregulin (AREG), and the transmembrane metalloproteinase AD-AM17, which can cleave and release AREG from the cell surface so that it may interact with its receptor. Tissue recombination and transplantation studies demonstrate that EGFR phosphorylation and ductal development proceed only when ADAM17 and AREG are expressed on mammary epithelial cells and EGFR is present on stromal cells, and that local administration of soluble AREG can rescue the development of ADAM17-deficient transplants. Thus proper mammary morphogenesis requires the ADAM17-mediated release of AREG from ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and EGFR-dependent stromal responses that in return elicit a new set of epithelial responses, all culminating in the formation of a fully functional ductal tree. This, however, raises new issues concerning what may act upstream, downstream or in parallel with the ADAM17-AREG-EGFR axis, how it may become hijacked or corrupted during the onset and evolution of cancer, and how such ill effects may be confronted.

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Section: Epithelial Adam17 Is Required For Mammary Developmentmentioning

confidence: 99%

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

Sternlicht

Sunnarborg

2008

J Mammary Gland Biol Neoplasia

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“…In contrast, NegGM, a structurally similar compound without metalloprotease inhibitory activity, did not inhibit TNF-a-induced phosphorylation of ERK1/2 as well as phosphorylation of NF-kB ( Figure 6A). It has recently been demonstrated that shedding of EGFR ligands is mediated by some members of the ADAMs family of metalloproteases, especially ADAM17 (Hinkle et al, 2004;Sahin et al, 2004). We therefore examined the effect of TAPI-1, an ADAMs inihibitor.…”

Section: Effects Of Metalloprotease Inhibitors On Tnf-a-induced Cellumentioning

confidence: 99%

Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib

et al. 2005

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We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-a (TNF-a) signalling pathways. Real-time reverse transcription -polymerase chain reaction showed that TNF-a mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF-but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-a-induced activation of MAPKs and Akt. In addition, TNF-a-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin av, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-a-induced responses except for NF-kB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-a. These results suggest that the TNF-a signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.

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“…Similarly, the TACE cleavage site in the growth hormone receptor also resides in a structurally similar JM region (Baumann and Frank, 2002). It appears that both stalk length and sequence are critical determinants of TACE cleavage (Hinkle et al, 2004). Further experimentation is needed to determine whether TACE is indeed responsible for JM cleavage of IFNaR2, and to determine the actual cleavage site.…”

Section: Discussionmentioning

confidence: 99%

Regulated proteolysis of the IFNaR2 subunit of the interferon-alpha receptor

et al. 2004

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The type I interferons (IFNs) bind surface receptors, induce JAK kinases and activate STAT transcription factors to stimulate the transcription of genes downstream of IFN-stimulated response elements (ISREs). In this study, we demonstrate that IFNaR2, a subunit of the type I IFN receptor, is proteolytically cleaved in a regulated manner. Immunoblotting shows that multi-step cleavage occurs in response to phorbol ester (PMA) and IFN-a, generating both a transmembrane 'stub' and the intracellular domain (ICD), similar to Notch proteolysis. Isolated membrane fractions process IFNaR2 to release the ICD. A chimeric receptor construct is utilized to show that cleavage requires the presenilins and occurs in response to epidermal growth factor and protein kinase C-d overexpression, as well as PMA and type I IFNs. Fluorescence microscopy demonstrates that a green fluorescent protein-ICD fusion localizes predominantly to the nucleus. A fusion between the ICD and the Gal4 DNA-binding domain represses transcription, in a histone deacetylasedependent manner, of a Gal4 upstream activating sequence-regulated reporter, while overexpression of the ICD alone represses transcription of a reporter linked to an ISRE. Proteolytic cleavage events may facilitate receptor turnover or, more likely, function as a mechanism for signaling similar to that employed by Notch and the Alzheimer's precursor protein.

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Selective Roles for Tumor Necrosis Factor α-converting Enzyme/ADAM17 in the Shedding of the Epidermal Growth Factor Receptor Ligand Family

Cited by 133 publications

References 81 publications

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer

Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib

Regulated proteolysis of the IFNaR2 subunit of the interferon-alpha receptor

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