作者
Katja Linher-Melville, Manu Sharma, Peter Nakhla, Elena Kum, Robert Ungard, Ji Park, David Rosa, Patrick Gunning, Gurmit Singh
发表日期
2019/1
期刊
Molecular Pain
卷号
15
页码范围
1744806918823477
出版商
SAGE Publications
简介
Aggressive breast cancer subtypes utilize system xc−, a membrane antiporter, to import cystine for glutathione synthesis and maintenance of redox homeostasis, in turn releasing glutamate as a metabolic pro-nociceptive by-product. Metastatic breast cancers establish themselves at distal sites including bone, where changes in extracellular glutamate levels contribute to cancer-induced bone pain. We previously established that stearically blocking system xc− activity with sulfasalazine delays the onset of nociceptive behaviours and that xCT, the functional antiporter subunit, is positively regulated by signal transducer and activator of transcription 3 (STAT3). In the current investigation, a murine xenograft cancer-induced bone pain model was applied to examine whether pharmacological inhibition of phosphorylated STAT3 (pSTAT3) induces changes in nociception. A high glutamate-releasing, xCT/pSTAT3 over …
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K Linher-Melville, M Sharma, P Nakhla, E Kum… - Molecular Pain, 2019