ArticleCell reports2022
De novo sphingolipid biosynthesis necessitates detoxification in cancer cells.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- SPTLC2-driven sphingolipid reprogramming of neutrophils impairs anti-tumour immunity and drives liver cancer progression.Oncogene · 2026Article
- Proteome Responses to Acute Inhibition of De Novo Sphingolipid Synthesis Suggest Cancer Combination Therapies.Cancers · 2026Article
- Review
- Don't Be Surprised When These Surprise You: Some Infrequently Studied Sphingoid Bases, Metabolites, and Factors That Should Be Kept in Mind During Sphingolipidomic Studies.International journal of molecular sciences · 2025Review
- Glucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin.International journal of molecular sciences · 2024Article
- Excavation of gene markers associated with pancreatic ductal adenocarcinoma based on interrelationships of gene expression.IET systems biology · 2024Article
- Patterns of Aneuploidy and Signaling Consequences in Cancer.Cancer research · 2024Review
- Sphingolipids: Less Enigmatic but Still Many Questions about the Role(s) of Ceramide in the Synthesis/Function of the Ganglioside Class of Glycosphingolipids.International journal of molecular sciences · 2024Review
- Selenium reduction of ubiquinone via SQOR suppresses ferroptosis.Nature metabolism · 2024Article
- Disruption of sugar nucleotide clearance is a therapeutic vulnerability of cancer cells.Nature · 2023Article
- The Critical Impact of Sphingolipid Metabolism in Breast Cancer Progression and Drug Response.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Sphingolipids play important signaling and structural roles in cells. Here, we find that during de novo sphingolipid biosynthesis, a toxic metabolite is formed with critical implications for cancer cell survival. The enzyme catalyzing the first step in this pathway, serine palmitoyltransferase complex (SPT), is upregulated in breast and other cancers. SPT is dispensable for cancer cell proliferation, as sphingolipids can be salvaged from the environment. However, SPT activity introduces a liability as its product, 3-ketodihydrosphingosine (3KDS), is toxic and requires clearance via the downstream enzyme 3-ketodihydrosphingosine reductase (KDSR). In cancer cells, but not normal cells, targeting KDSR induces toxic 3KDS accumulation leading to endoplasmic reticulum (ER) dysfunction and loss of proteostasis. Furthermore, the antitumor effect of KDSR disruption can be enhanced by increasing metabolic input (via high-fat diet) to allow greater 3KDS production. Thus, de novo sphingolipid biosynthesis entails a detoxification requirement in cancer cells that can be therapeutically exploited.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.