Hypoxia induced deregulation of sphingolipids in colon cancer is a prognostic marker for patient outcome.
Biomarker
Lipidomic
Metabolism
Oxidative consumption rate, hypoxia
Proteomic
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
01 2024
01 2024
Historique:
received:
29
06
2023
revised:
26
09
2023
accepted:
27
09
2023
medline:
13
11
2023
pubmed:
7
10
2023
entrez:
6
10
2023
Statut:
ppublish
Résumé
Sphingolipids are important for the physicochemical properties of cellular membranes and deregulated in tumors. In human colon cancer tissue ceramide synthase (CerS) 4 and CerS5 are reduced which correlates with a reduced survival probability of late-stage colon cancer patients. Both enzymes are reduced after hypoxia in advanced colorectal cancer (CRC) cells (HCT-116, SW620) but not in non-metastatic CRC cells (SW480, Caco-2). Downregulation of CerS4 or CerS5 in advanced CRC cells enhanced tumor formation in nude mice and organoid growth in vitro. This was accompanied by an enhanced proliferation rate and metabolic changes leading to a shift towards the Warburg effect. In contrast, CerS4 or CerS5 depletion in Caco-2 cells reduced tumor growth in vivo. Lipidomic and proteomic analysis of membrane fractions revealed significant changes in tumor-promoting cellular pathways and cellular transporters. This study identifies CerS4 and CerS5 as prognostic markers for advanced colon cancer patients and provides a comprehensive overview about the associated cellular metabolic changes. We propose that the expression level of CerS4 and CerS5 in colon tumors could serve as a basis for decision-making for personalized treatment of advanced colon cancer patients. Trial registration: The study was accredited by the study board of the Deutsche Krebsgesellschaft (Registration No: St-D203, 2017/06/30, retrospectively registered).
Identifiants
pubmed: 37802156
pii: S0925-4439(23)00272-7
doi: 10.1016/j.bbadis.2023.166906
pii:
doi:
Substances chimiques
Sphingolipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166906Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Klaus Scholich reports financial support was provided by German Research Foundation. Andreas Weigert reports financial support was provided by German Research Foundation. Bernhard Brune reports financial support was provided by German Research Foundation. Gerd Geisslinger reports financial support was provided by German Research Foundation. Ilka Wittig reports financial support was provided by German Research Foundation. Sabine Grosch reports financial support was provided by Fraunhofer Cluster of Excellence for Immune-Mediated Diseases. Sabine Grosch reports financial support was provided by German Research Foundation. Thomas Deller reports financial support was provided by Novartis AG.