@article {Drexlere202000903, author = {Konstantin Drexler and Katharina M Schmidt and Katrin Jordan and Marianne Federlin and Vladimir M Milenkovic and Gerhard Liebisch and Anna Artati and Christian Schmidl and Gregor Madej and Janina Tokarz and Alexander Cecil and Wolfgang Jagla and Silke Haerteis and Thiha Aung and Christine Wagner and Maria Kolodziejczyk and Stefanie Heinke and Evan H Stanton and Barbara Schwertner and Dania Riegel and Christian H Wetzel and Wolfgang Buchalla and Martin Proescholdt and Christoph A Klein and Mark Berneburg and Hans J Schlitt and Thomas Brabletz and Christine Ziegler and Eric K Parkinson and Andreas Gaumann and Edward K Geissler and Jerzy Adamski and Sebastian Haferkamp and Maria E Mycielska}, title = {Cancer-associated cells release citrate to support tumour metastatic progression}, volume = {4}, number = {6}, elocation-id = {e202000903}, year = {2021}, doi = {10.26508/lsa.202000903}, publisher = {Life Science Alliance}, abstract = {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{\textquoteright}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.}, URL = {https://www.life-science-alliance.org/content/4/6/e202000903}, eprint = {https://www.life-science-alliance.org/content/4/6/e202000903.full.pdf}, journal = {Life Science Alliance} }