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 was...

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Published inFrontiers in endocrinology (Lausanne) Vol. 11; p. 621944
Main Authors Liu, Chien-Liang, Cheng, Shih-Ping, Chen, Ming-Jen, Lin, Chi-Hsin, Chen, Shan-Na, Kuo, Yi-Hue, Chang, Yuan-Ching
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 04.02.2021
Subjects
breast cancer
Endocrinology
myosin light chain
NAD
neoplasm invasiveness
quinolinate phosphoribosyltransferase
NAD
breast cancer
myosin light chain
neoplasm invasiveness
quinolinate phosphoribosyltransferase
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Abstract 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 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.
AbstractList 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 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.
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.
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.
Author Chen, Ming-Jen
Kuo, Yi-Hue
Chen, Shan-Na
Liu, Chien-Liang
Chang, Yuan-Ching
Cheng, Shih-Ping
Lin, Chi-Hsin
AuthorAffiliation 1 Department of Surgery, MacKay Memorial Hospital , Taipei , Taiwan
3 Department of Medical Research, MacKay Memorial Hospital , Taipei , Taiwan
2 Department of Surgery, School of Medicine, Mackay Medical College , New Taipei City , Taiwan
4 Department of Bioscience Technology, Chung Yuan Christian University , Taoyuan City , Taiwan
AuthorAffiliation_xml – name: 4 Department of Bioscience Technology, Chung Yuan Christian University , Taoyuan City , Taiwan
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Keywords NAD
breast cancer
myosin light chain
neoplasm invasiveness
quinolinate phosphoribosyltransferase
Language English
License Copyright © 2021 Liu, Cheng, Chen, Lin, Chen, Kuo and Chang.
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Edited by: Ralf Jockers, Université de Paris, France
This article was submitted to Cellular Endocrinology, a section of the journal Frontiers in Endocrinology
Reviewed by: Jean-Marc Vanacker, Centre National de la Recherche Scientifique (CNRS), France; Guillermo Romero, University of Pittsburgh, United States
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Snippet Perturbed Nicotinamide adenine dinucleotide (NAD ) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT)...
Perturbed Nicotinamide adenine dinucleotide (NAD + ) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT)...
Perturbed Nicotinamide adenine dinucleotide (NAD+) homeostasis is involved in cancer progression and metastasis. Quinolinate phosphoribosyltransferase (QPRT)...
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StartPage 621944
SubjectTerms breast cancer
Endocrinology
myosin light chain
NAD
neoplasm invasiveness
quinolinate phosphoribosyltransferase
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Title Quinolinate Phosphoribosyltransferase Promotes Invasiveness of Breast Cancer Through Myosin Light Chain Phosphorylation
URI https://www.ncbi.nlm.nih.gov/pubmed/33613454
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