Nicotinamide Phosphoribosyltransferase Promotes Epithelial-to-Mesenchymal Transition as a Soluble Factor Independent of Its Enzymatic Activity

Soncini, Debora; Caffa, Irene; Zoppoli, Gabriele; Cea, Michele; Cagnetta, Antonia; Passalacqua, Mario; Mastracci, Luca; Boero, Silvia; Montecucco, Fabrizio; Sociali, Giovanna; Lasigliè, Denise; Damonte, Patrizia; Grozio, Alessia; Mannino, Elena; Poggi, Alessandro; D’Agostino, Vito; Monacelli, Fiammetta; Provenzani, Alessandro; Odetti, Patrizio; Ballestrero, Alberto; Bruzzone, Santina; Nencioni, Alessio

doi:10.1074/jbc.m114.594721

Cited by 71 publications

(59 citation statements)

References 51 publications

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“…This finding is consistent with previous studies [35,36]. Involvement of different mechanisms have been reported in extracellular visfatin-mediated breast cancer growth and metastatic potential including cyclin D1 and cyclindependent kinase 2 (CDK2) [35], NF-κB and Notch1 [37], (transforming growth factor β (TGF-β) [38] or c-Abl and STAT3 signaling [36] pathways. Here we showed that PI3K/AKT and MAPK/ERK pathways are important regulators in visfatin-induced proliferation of breast cancer cells such that inhibition of PI3K and MEK1/2 blocked cell proliferation that was enhanced by visfatin.…”

Section: Discussionsupporting

confidence: 93%

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

et al. 2017

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Section: Discussionsupporting

confidence: 93%

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

et al. 2017

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“…S3E and S3F). Other mechanisms reported in extracellular visfatin-mediated breast cancer growth and metastatic potential included cyclin D1 and cdk2 (44), NF-kB and Notch1 (45), or PI3K/Akt and TGFb (46). As the identity of "visfatin receptor" is not known to date, it limits our understanding for the molecular mechanisms of extracellular visfatin.…”

Section: Characterization Of the Biologic Effect Of Visfatin On Breasmentioning

confidence: 94%

Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation

Hung

Hou

et al. 2016

Clinical Cancer Research

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Purpose: Visfatin is an adipocytokine involved in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings.Experimental Design: Associations of serum visfatin with clinicopathologic characteristics and patient survival were assessed with Cox regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were used to inhibit c-Abl and STAT3 activation, respectively.Results: Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatinpromoted in vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was observed in zebrafish xenografted with visfatin-pretreated breast cancer cells. Tumor growth and lung metastasis occurred in visfatin-administered mice xenografted with breast cancer cells. Tail vein-injected mice with visfatin-pretreated breast cancer cells showed increased lung metastasis, which was suppressed by imatinib.Conclusions: Serum visfatin levels in breast cancer patients reveal potential prognostic values, and our findings that visfatin promoted breast cancer through activation of c-Abl and STAT3 may provide an important molecular basis for future design of targeted therapies that take into account different serum visfatin levels in breast cancer.

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“…28 So the nonenzymatic action mode of extracellular NAMPT still remains to be exactly elucidated because numerous studies have reported that extracellular NAMPT is able to regulate cell events such as macrophage survival/polarization and epithelial-to-mesenchymal transition by an enzyme activity-independent manner. [38][39][40] …”

Section: Nampt and Nampt-controlled Nad Poolmentioning

confidence: 98%

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

Wang

Liu

et al. 2016

Journal of Cardiovascular Pharmacology

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Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

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Nicotinamide Phosphoribosyltransferase Promotes Epithelial-to-Mesenchymal Transition as a Soluble Factor Independent of Its Enzymatic Activity

Abstract: Background: Nicotinamide phosphoribosyltransferase (NAMPT) acts both as an enzyme in the production of the coenzyme NAD ϩ and as a secreted cytokine.

Cited by 71 publications

References 51 publications

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

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