Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer
- 1 June 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 80 (11), 2163-2174
- https://doi.org/10.1158/0008-5472.can-19-3177
Abstract
The metabolic network of sphingolipids plays important roles in cancer biology. Prominent sphingolipids include ceramides and sphingosine-1-phosphate that regulate multiple aspects of growth, apoptosis, and cellular signaling. Although a significant number of enzymatic regulators of the sphingolipid pathway have been described in detail, many remained poorly characterized. Here we applied a patient-derived systemic approach to identify and molecularly define progestin and adipoQ receptor family member IV (PAQR4) as a Golgi-localized ceramidase. PAQR4 was ~5-fold upregulated in breast cancer compared to matched control tissue and its overexpression correlated with disease-specific survival rates in breast cancer. Induction of PAQR4 in breast tumors was found to be subtype-independent and correlated with increased ceramidase activity. These findings establish PAQR4 as Golgi-localized ceramidase required for cellular growth in breast cancer.Keywords
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Funding Information
- NIH NCI (P30 CA016059)
- NIH (S10RR031535)
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