| First Author | Pedersen L | Year | 2020 |
| Journal | Cancer Res | Volume | 80 |
| Issue | 11 | Pages | 2163-2174 |
| PubMed ID | 32291319 | Mgi Jnum | J:352405 |
| Mgi Id | MGI:6431728 | Doi | 10.1158/0008-5472.CAN-19-3177 |
| Citation | Pedersen L, et al. (2020) Golgi-Localized PAQR4 Mediates Antiapoptotic Ceramidase Activity in Breast Cancer. Cancer Res 80(11):2163-2174 |
| abstractText | 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 approximately 5-fold upregulated in breast cancer compared with 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. SIGNIFICANCE: Induction of and cellular dependency on de novo sphingolipid synthesis via PAQR4 highlights a central vulnerability in breast cancer that may serve as a viable therapeutic target. |
