Summary of project PR001455

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001455. The data can be accessed directly via it's Project DOI: 10.21228/M8NH7M This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001455
Project DOI:doi: 10.21228/M8NH7M
Project Title:1-deoxysphingolipid synthesis compromises anchorage-independent growth and plasma membrane endocytosis in cancer cells
Project Type:Manuscript
Project Summary:Serine palmitoyltransferase (SPT) predominantly incorporates serine and fatty acyl-CoAs into diverse sphingolipids that serve as structural components of membranes and signaling molecules within or amongst cells. However, SPT also uses alanine as a substrate in the contexts of low serine availability, alanine accumulation, or disease-causing mutations in hereditary sensory neuropathy type I (HSAN1), resulting in the synthesis and accumulation of 1-deoxysphingolipids. These species promote cytotoxicity in neurons and impact diverse cellular phenotypes, including suppression of anchorage-independent cancer cell growth. While altered serine and alanine can promote 1-deoxysphingolipid synthesis, they impact numerous other metabolic pathways important for cancer cells. Here we combined isotope tracing, quantitative metabolomics, and functional studies to better understand the mechanistic drivers of 1-deoxysphingolipid toxicity in cancer cells. Both alanine treatment and SPTLC1C133W expression induce 1-deoxy(dihydro)ceramide synthesis and accumulation but fail to broadly impact intermediary metabolism, abundances of other lipids, or growth of adherent cells. However, spheroid culture and soft agar colony formation were compromised when endogenous 1-deoxysphingolipid synthesis was induced via SPTLC1C133W expression. Consistent with these impacts on anchorage-independent cell growth, we observed that 1-deoxysphingolipid synthesis reduced plasma membrane endocytosis. These results highlight a potential role for SPT promiscuity in linking altered amino acid metabolism to plasma membrane endocytosis.
Institute:TU Braunschweig
Last Name:Cordes
First Name:Thekla
Address:Rebenring 56, Braunschweig, Lower Saxony, 38106, Germany
Funding Source:NIH NCI R01CA234245 and R50CA252146
Publications:JLR accepted
Contributors:Thekla Cordes (University of California San Diego; Salk Institute for Biological Studies; TU Braunschweig), Christian Metallo (University of California, San Diego; Salk Institute for Biological Studies)

Summary of all studies in project PR001455

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002274 1-deoxysphingolipid synthesis compromises anchorage-independent growth and plasma membrane endocytosis in cancer cells Homo sapiens Salk Institute for Biological Studies MS 2022-09-16 1 18 Uploaded data (1.4G)*