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Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation
Perturbed Nicotinamide adenine dinucleotide (NAD(+)) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD(+) generation. In this study, we demonstrated that QPRT expressio...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890081/ https://www.ncbi.nlm.nih.gov/pubmed/33613454 http://dx.doi.org/10.3389/fendo.2020.621944 |
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author | Liu, Chien-Liang Cheng, Shih-Ping Chen, Ming-Jen Lin, Chi-Hsin Chen, Shan-Na Kuo, Yi-Hue Chang, Yuan-Ching |
author_facet | Liu, Chien-Liang Cheng, Shih-Ping Chen, Ming-Jen Lin, Chi-Hsin Chen, Shan-Na Kuo, Yi-Hue Chang, Yuan-Ching |
author_sort | Liu, Chien-Liang |
collection | PubMed |
description | Perturbed Nicotinamide adenine dinucleotide (NAD(+)) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD(+) generation. In this study, we demonstrated that QPRT expression was upregulated in invasive breast cancer and spontaneous mammary tumors from MMTV-PyVT transgenic mice. Knockdown of QPRT expression inhibited breast cancer cell migration and invasion. Consistently, ectopic expression of QPRT promoted cell migration and invasion in breast cancer cells. Treatment with QPRT inhibitor (phthalic acid) or P2Y(11) antagonist (NF340) could reverse the QPRT-induced invasiveness and phosphorylation of myosin light chain. Similar reversibility could be observed following treatment with Rho inhibitor (Y16), ROCK inhibitor (Y27632), PLC inhibitor (U73122), or MLCK inhibitor (ML7). Altogether, these results indicate that QPRT enhanced breast cancer invasiveness probably through purinergic signaling and might be a potential prognostic indicator and therapeutic target in breast cancer. |
format | Online Article Text |
id | pubmed-7890081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78900812021-02-19 Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation Liu, Chien-Liang Cheng, Shih-Ping Chen, Ming-Jen Lin, Chi-Hsin Chen, Shan-Na Kuo, Yi-Hue Chang, Yuan-Ching Front Endocrinol (Lausanne) Endocrinology Perturbed Nicotinamide adenine dinucleotide (NAD(+)) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT) is the rate-limiting enzyme in the kynurenine pathway participating in NAD(+) generation. In this study, we demonstrated that QPRT expression was upregulated in invasive breast cancer and spontaneous mammary tumors from MMTV-PyVT transgenic mice. Knockdown of QPRT expression inhibited breast cancer cell migration and invasion. Consistently, ectopic expression of QPRT promoted cell migration and invasion in breast cancer cells. Treatment with QPRT inhibitor (phthalic acid) or P2Y(11) antagonist (NF340) could reverse the QPRT-induced invasiveness and phosphorylation of myosin light chain. Similar reversibility could be observed following treatment with Rho inhibitor (Y16), ROCK inhibitor (Y27632), PLC inhibitor (U73122), or MLCK inhibitor (ML7). Altogether, these results indicate that QPRT enhanced breast cancer invasiveness probably through purinergic signaling and might be a potential prognostic indicator and therapeutic target in breast cancer. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7890081/ /pubmed/33613454 http://dx.doi.org/10.3389/fendo.2020.621944 Text en Copyright © 2021 Liu, Cheng, Chen, Lin, Chen, Kuo and Chang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Liu, Chien-Liang Cheng, Shih-Ping Chen, Ming-Jen Lin, Chi-Hsin Chen, Shan-Na Kuo, Yi-Hue Chang, Yuan-Ching Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation |
title | Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation |
title_full | Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation |
title_fullStr | Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation |
title_full_unstemmed | Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation |
title_short | Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation |
title_sort | quinolinate phosphoribosyltransferase promotes invasiveness of breast cancer through myosin light chain phosphorylation |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890081/ https://www.ncbi.nlm.nih.gov/pubmed/33613454 http://dx.doi.org/10.3389/fendo.2020.621944 |
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