کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8320749 | 1539405 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nicotinamide phosphoribosyltransferase can affect metastatic activity and cell adhesive functions by regulating integrins in breast cancer
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کلمات کلیدی
AMPSCIDNRKNARNAMPTERKnicotinic acid mononucleotideshRNAPARPsmTORC1uPARBRCA2MMTV-PyMTMMPαvβ3NAD+ - NAD +Nmnat - NMNATsmall hairpin RNA - RNA کوچک موی سرAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPadenosine monophosphate - آدنوزین مونوفسفرهNdi1 - این 1 استIntegrins - اینتگرینNicotinamide riboside - ریبوباید نیکوتینامیدbreast cancer 2 - سرطان سینه 2Breast cancer - سرطان پستانbreast cancer 1 - سرطان پستان 1Vascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)Metastasis - متاستاز Matrix metalloproteinases - متالوپروتئیناز ماتریکسNADH - نادانNaMN - نامnicotinamide adenine dinucleotide - نیکوتین آمید adenine dinucleotidenicotinamide phosphoribosyltransferase - نیکوتین آمید فسفریبوسیل ترانسفرازnicotinamide mononucleotide - نیکوتین آمید مونونوکلئوتیدMammalian target of rapamycin complex 1 - هدف پستانداران مجتمع رپامایسین 1BRCA1 - ژن BRCA1reduced nicotinamide adenine dinucleotide - کاهش ninocotinamide adenine dinucleotidesevere combined immunodeficiency - کمبود شدید مصدومextracellular signal-regulated kinases - کیناز های تنظیم شده سیگنال خارج سلولیUrokinase plasminogen activator receptor - گیرنده فعال کننده پلاسمینوژن اورو کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Nicotinamide phosphoribosyltransferase can affect metastatic activity and cell adhesive functions by regulating integrins in breast cancer Nicotinamide phosphoribosyltransferase can affect metastatic activity and cell adhesive functions by regulating integrins in breast cancer](/preview/png/8320749.png)
چکیده انگلیسی
NAD+ metabolism is an essential regulator of cellular redox reactions, energy pathways, and a substrate provider for NAD+ consuming enzymes. We recently demonstrated that enhancement of NAD+/NADH levels in breast cancer cells with impaired mitochondrial NADH dehydrogenase activity, through augmentation of complex I or by supplementing tumor cell nutrients with NAD+ precursors, inhibits tumorigenicity and metastasis. To more fully understand how aberrantly low NAD+ levels promote tumor cell dissemination, we here asked whether inhibition of NAD+ salvage pathway activity by reduction in nicotinamide phosphoribosyltransferase (NAMPT) expression can impact metastasis and tumor cell adhesive functions. We show that knockdown of NAMPT, the enzyme catalyzing the rate-limiting step of the NAD+ salvage pathway, enhances metastatic aggressiveness in human breast cancer cells and involves modulation of integrin expression and function. Reduction in NAMPT expression is associated with upregulation of select adhesion receptors, particularly αvβ3 and β1 integrins, and results in increased breast cancer cell attachment to extracellular matrix proteins, a key function in tumor cell dissemination. Interestingly, NAMPT downregulation prompts expression of integrin αvβ3 in a high affinity conformation, known to promote tumor cell adhesive interactions during hematogenous metastasis. NAMPT has been selected as a therapeutic target for cancer therapy based on the essential functions of this enzyme in NAD+ metabolism, cellular redox, DNA repair and energy pathways. Notably, our results indicate that incomplete inhibition of NAMPT, which impedes NAD+ metabolism but does not kill a tumor cell can alter its phenotype to be more aggressive and metastatic. This phenomenon could promote cancer recurrence, even if NAMPT inhibition initially reduces tumor growth.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 23, November 2014, Pages 79-87
Journal: DNA Repair - Volume 23, November 2014, Pages 79-87
نویسندگان
Antonio F. Santidrian, Sarah E. LeBoeuf, Erik D. Wold, Melissa Ritland, Jane S. Forsyth, Brunhilde H. Felding,