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 expression wa...
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| Format: | Article |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2020.621944/full |
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| author | Chien-Liang Liu Chien-Liang Liu Chien-Liang Liu Shih-Ping Cheng Shih-Ping Cheng Shih-Ping Cheng Ming-Jen Chen Ming-Jen Chen Ming-Jen Chen Chi-Hsin Lin Chi-Hsin Lin Shan-Na Chen Yi-Hue Kuo Yuan-Ching Chang Yuan-Ching Chang Yuan-Ching Chang |
| author_facet | Chien-Liang Liu Chien-Liang Liu Chien-Liang Liu Shih-Ping Cheng Shih-Ping Cheng Shih-Ping Cheng Ming-Jen Chen Ming-Jen Chen Ming-Jen Chen Chi-Hsin Lin Chi-Hsin Lin Shan-Na Chen Yi-Hue Kuo Yuan-Ching Chang Yuan-Ching Chang Yuan-Ching Chang |
| author_sort | Chien-Liang Liu |
| collection | DOAJ |
| 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 P2Y11 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. |
| first_indexed | 2024-12-24T04:50:20Z |
| format | Article |
| id | doaj.art-03583c902fb34f01a65a360337d0bdf0 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-24T04:50:20Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-03583c902fb34f01a65a360337d0bdf02022-12-21T17:14:33ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-02-011110.3389/fendo.2020.621944621944Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain PhosphorylationChien-Liang Liu0Chien-Liang Liu1Chien-Liang Liu2Shih-Ping Cheng3Shih-Ping Cheng4Shih-Ping Cheng5Ming-Jen Chen6Ming-Jen Chen7Ming-Jen Chen8Chi-Hsin Lin9Chi-Hsin Lin10Shan-Na Chen11Yi-Hue Kuo12Yuan-Ching Chang13Yuan-Ching Chang14Yuan-Ching Chang15Department of Surgery, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, School of Medicine, Mackay Medical College, New Taipei City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, School of Medicine, Mackay Medical College, New Taipei City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, School of Medicine, Mackay Medical College, New Taipei City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Surgery, School of Medicine, Mackay Medical College, New Taipei City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanPerturbed 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 P2Y11 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.https://www.frontiersin.org/articles/10.3389/fendo.2020.621944/fullquinolinate phosphoribosyltransferaseNADmyosin light chainneoplasm invasivenessbreast cancer |
| spellingShingle | Chien-Liang Liu Chien-Liang Liu Chien-Liang Liu Shih-Ping Cheng Shih-Ping Cheng Shih-Ping Cheng Ming-Jen Chen Ming-Jen Chen Ming-Jen Chen Chi-Hsin Lin Chi-Hsin Lin Shan-Na Chen Yi-Hue Kuo Yuan-Ching Chang Yuan-Ching Chang Yuan-Ching Chang Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation Frontiers in Endocrinology quinolinate phosphoribosyltransferase NAD myosin light chain neoplasm invasiveness breast cancer |
| 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 | quinolinate phosphoribosyltransferase NAD myosin light chain neoplasm invasiveness breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2020.621944/full |
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