Selective Use of ADAM10 and ADAM17 in Activation of Notch1 Signaling

Çağavı, Esra; Weinmaster, Gerry

doi:10.1128/mcb.00406-09

Cited by 280 publications

(257 citation statements)

References 62 publications

Supporting

Mentioning

242

Contrasting

Order By: Relevance

“…We also identified S1P-induced Notch activation without Notch ligands. Consistent with our observations, previous studies have shown that ADAM17 mediates ligand-independent Notch activation, while ADAM10 is ligand dependent 38,39 . Another study has shown that soluble form of Jagged1 activates Notch signalling without cell-cell contact 40 .…”

Section: Discussionsupporting

confidence: 82%

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

et al. 2014

View full text Add to dashboard Cite

Many tumours originate from cancer stem cells (CSCs), which is a small population of cells that display stem cell properties. However, the molecular mechanisms that regulate CSC frequency remain poorly understood. Here, using microarray screening in aldehyde dehydrogenase (ALDH)-positive CSC model, we identify a fundamental role for a lipid mediator sphingosine-1-phosphate (S1P) in CSC expansion. Stimulation with S1P enhances ALDH-positive CSCs via S1P receptor 3 (S1PR3) and subsequent Notch activation. CSCs overexpressing sphingosine kinase 1 (SphK1), an S1P-producing enzyme, show increased ability to develop tumours in nude mice, compared with parent cells or CSCs. Tumorigenicity of CSCs overexpressing SphK1 is inhibited by S1PR3 knockdown or S1PR3 antagonist. Breast cancer patient-derived mammospheres contain SphK1 þ /ALDH1 þ cells or S1PR3 þ /ALDH1 þ cells. Our findings provide new insights into the lipid-mediated regulation of CSCs via Notch signalling, and rationale for targeting S1PR3 in cancer.

show abstract

Section: Discussionsupporting

confidence: 82%

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

et al. 2014

View full text Add to dashboard Cite

show abstract

“…TNF-a has been reported to show an increased expression in OSCC specimens 27 and promote S2 cleavage (resulting in NICD Notch1 in oral squamous cell carcinoma R Yoshida et al production) via TACE maturation in Notch signaling. [28][29][30] As shown in Figure 5, NICD cleavages were observed in a TNF-a concentration-dependent manner. In addition, NICD cleavage was inhibited by GSI treatment.…”

Section: Tnf A-dependent Oscc Cell Invasivenessmentioning

confidence: 90%

The pathological significance of Notch1 in oral squamous cell carcinoma

Yoshida

Nagata

Nakayama

et al. 2013

Laboratory Investigation

102

View full text Add to dashboard Cite

“…Notch is a putative substrate of ADAM-10 and ADAM-17 [59] and, therefore, its possible inactivation by GM6001 may enhance neuroblast generation in the injured tissue.…”

Section: Implication Of Adam-17/tgf-a/egfr In the Creation Of A Non-nmentioning

confidence: 99%

ADAM-17/Tumor Necrosis Factor-α-Converting Enzyme Inhibits Neurogenesis and Promotes Gliogenesis from Neural Stem Cells

et al. 2011

View full text Add to dashboard Cite

Neural precursor cells (NPCs) are activated in central nervous system injury. However, despite being multipotential, their progeny differentiates into astrocytes rather than neurons in situ. We have investigated the role of epidermal growth factor receptor (EGFR) in the generation of non-neurogenic conditions. Cultured mouse subventricular zone NPCs exposed to differentiating conditions for 4 days generated approximately 50% astrocytes and 30% neuroblasts. Inhibition of EGFR with 4-(3-chloroanilino)-6,7-dimethoxyquinazoline significantly increased the number of neuroblasts and decreased that of astrocytes. The same effects were observed upon treatment with the metalloprotease inhibitor galardin, N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide (GM 6001), which prevented endogenous transforming growth factor-a (TGF-a) release. These results suggested that metalloprotease-dependent EGFRligand shedding maintained EGFR activation and favored gliogenesis over neurogenesis. Using a disintegrin and metalloprotease 17 (ADAM-17) small interference RNAs transfection of NPCs, ADAM-17 was identified as the metalloprotease involved in cell differentiation in these cultures. In vivo experiments revealed a significant upregulation of ADAM-17 mRNA and de novo expression of ADAM-17 protein in areas of cortical injury in adult mice. Local NPCs, identified by nestin staining, expressed high levels of ADAM-17, as well as TGF-a and EGFR, the three molecules necessary to prevent neurogenesis and promote glial differentiation in vitro. Chronic local infusions of GM6001 resulted in a notable increase in the number of neuroblasts around the lesion. These results indicate that, in vivo, the activation of a metalloprotease, most probably ADAM-17, initiates EGFR-ligand shedding and EGFR activation in an autocrine manner, preventing the generation of new neurons from NPCs. Inhibition of ADAM-17, the limiting step in this sequence, may contribute to the generation of neurogenic niches in areas of brain damage.

show abstract

Selective Use of ADAM10 and ADAM17 in Activation of Notch1 Signaling

Cited by 280 publications

References 62 publications

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

The pathological significance of Notch1 in oral squamous cell carcinoma

ADAM-17/Tumor Necrosis Factor-α-Converting Enzyme Inhibits Neurogenesis and Promotes Gliogenesis from Neural Stem Cells

Contact Info

Product

Resources

About