Golgi-localized PAQR4 mediates anti-apoptotic Ceramidase activity in breast cancer

Line Pedersen, Pouda Panahandeh, Muntequa Ishtiaq Siraji, Stian Knappskog, Per Eystein Lønning, Qingzhang Zhu, Ruth Gordillo, Philipp E. Scherer, Anders Molven, Knut Teigen, Nils Halberg

Research output: Contribution to journalArticlepeer-review

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 many significant enzymatic regulators of the sphingolipid pathway have been described in detail, the list is currently incomplete. Here, we applied a systemic approach to identify and molecularly define progestin and adipoQ receptor family member IV (PAQR4) as a Golgi-localized ceramidase. We find PAQR4 to be ~5 fold upregulated in breast cancer compared to matched control tissue and that its overexpression correlate with disease-specific survival rates in breast cancer. PAQR4 is a seven transmembrane protein, and depletion of PAQR4 leads to cellular apoptosis through accumulation of ceramides. Our findings establish PAQR4 as Golgi-localized ceramidase required for cellular growth in breast cancer.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Sep 18 2019

Keywords

  • Breast Cancer
  • Ceramidase
  • Golgi
  • PAQR4
  • Sphingolipids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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