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Drexler, K.* ; Schmidt, K.M.* ; Jordan, K.* ; Federlin, M.* ; Milenkovic, V.M.* ; Liebisch, G.* ; Artati, A. ; Schmidl, C.* ; Madej, G.* ; Tokarz, J. ; Cecil, A. ; Jagla, W.* ; Haerteis, S.* ; Aung, T.* ; Wagner, C.* ; Kolodziejczyk, M.* ; Heinke, S.* ; Stanton, E.H.* ; Schwertner, B.* ; Riegel, D.* ; Wetzel, C.H.* ; Buchalla, W.* ; Proescholdt, M.* ; Klein, C.A.* ; Berneburg, M.* ; Schlitt, H.J.* ; Brabletz, T.* ; Ziegler, C.* ; Parkinson, E.K.* ; Gaumann, A.* ; Geissler, E.K.* ; Adamski, J. ; Haferkamp, S.* ; Mycielska, M.E.*

Cancer-associated cells release citrate to support tumour metastatic progression.

Life Sci. All. 4:e202000903 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Citrate is important for lipid synthesis and epigenetic regulation in addition to ATP production. We have previously reported that cancer cells import extracellular citrate via the pmCiC transporter to support their metabolism. Here, we show for the first time that citrate is supplied to cancer by cancer-associated stroma (CAS) and also that citrate synthesis and release is one of the latter's major metabolic tasks. Citrate release from CAS is controlled by cancer cells through cross-cellular communication. The availability of citrate from CAS regulated the cytokine profile, metabolism and features of cellular invasion. Moreover, citrate released by CAS is involved in inducing cancer progression especially enhancing invasiveness and organ colonisation. In line with the in vitro observations, we show that depriving cancer cells of citrate using gluconate, a specific inhibitor of pmCiC, significantly reduced the growth and metastatic spread of human pancreatic cancer cells in vivo and muted stromal activation and angiogenesis. We conclude that citrate is supplied to tumour cells by CAS and citrate uptake plays a significant role in cancer metastatic progression.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Tandem Mass-spectrometry; High-throughput Quantification; Tgf-beta; Microenvironment; Migration; Metabolism; Interleukin-6; Fibroblasts; Regulator; Phenotype
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Journal Life Science Alliance
Quellenangaben Volume: 4, Issue: 6, Pages: , Article Number: e202000903 Supplement: ,
Publisher EMBO Press
Publishing Place Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Molekulare Endokrinologie und Metabolismus (MEM)
Grants ReFoRmC
Else-Kroner-Fresenius-Stiftung grant
Deutsche Forschungsgemeinschaft (DFG) grant