Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL

Research output: Contribution to journalJournal articlepeer-review

Documents

  • Fulltext

    Final published version, 2.23 MB, PDF document

Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin’s primary cutaneous T cell lymphomas, with Mycosis Fungoides and Sézary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) is a crucial enzyme that catalyses the biosynthesis of fatty acids, which has been reported to play an oncogenic role in various malignancies but not in CTCL so far. Herein, we show that FASN is highly expressed in CTCL cell lines and in peripheral blood mononuclear cells (PBMCs) from CTCL patients, while it is not in PBMCs from healthy individuals. The inhibition of FASN in CTCL cell lines impairs cell viability, survival, and proliferation, but, interestingly, it also increases FASN expression. However, inhibiting sterol regulatory element binding protein (SREBP), a transcription factor that promotes the expression of FASN, partially reversed the upregulation of FASN induced by FASN inhibitors. Thus, the combination of FASN and SREBP inhibitors enhanced the effects on both CTCL cell lines and PBMCs from SS patients, where a valid inhibition on cell proliferation could be verified. Importantly, compared to non-malignant cells, primary malignant cells are more sensitive to the inhibition of FASN and SREBP, making the combination of FASN and SREBP inhibitors a promising novel therapeutic strategy in CTCL.

Original languageEnglish
Article number4491
JournalCancers
Volume14
Issue number18
ISSN2072-6694
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

    Research areas

  • cancer therapy, CTCL, FASN, SREBP

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 323858938