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 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.
Highlights
Breast cancer is the most common malignant disease among women and represents a major healthcare burden [1]
These results indicate that the RhoROCK and Phospholipase C (PLC)-myosin light chain kinase (MLCK) pathways are both involved in the phosphorylation of myosin light chain as a downstream of the P2Y11 activation
We provided strong evidence supporting the association between Quinolinate phosphoribosyltransferase (QPRT) upregulation and tumor progression in breast cancer
Summary
Breast cancer is the most common malignant disease among women and represents a major healthcare burden [1]. The incidence of breast cancer has been increasing worldwide, including in Taiwan [2, 3]. Despite tremendous advances in the diagnosis and treatment of breast cancer, an increase in breast cancer mortality rates without regional disparities has been observed [4]. Developing new therapeutic strategies that target cancer progression and metastasis will be essential to improve patient outcomes. Nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH play an important role in biogenesis and redox balance of the human body [5].
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