%0 Journal Article %1 heering201210115800085472can113069 %A Heering, Johanna %A Weis, Nicole %A Holeiter, Monika %A Neugart, Felix %A Staebler, Annette %A Fehm, Tanja N. %A Bischoff, Annabell %A Schiller, Jürgen %A Duss, Stephan %A Schmid, Simone %A Korte, Thomas %A Herrmann, Andreas %A Olayioye, Monilola A %D 2012 %J Cancer Research %K 2012 izi olayioye %N 11 %P 2855--2866 %R 10.1158/0008-5472.CAN-11-3069 %T Loss of the ceramide transfer protein augments EGF receptor signaling in breast cancer %U http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008-5472.CAN-11-3069 %V 72 %X Triple-negative breast cancers (TNBC) are especially refractory to treatment due to their negative hormone receptor and ErbB2/HER2 status. Therefore, the identification of cancer-associated deregulated signaling pathways is necessary to develop improved targeted therapies. Here, we show that expression of the ceramide transfer protein CERT is reduced in TNBCs. CERT transfers ceramide from the endoplasmic reticulum to the Golgi complex for conversion into sphingomyelin (SM). We provide evidence that by regulating cellular SM levels, CERT determines the signaling output of the EGF receptor (EGFR/ErbB1), which is upregulated in approximately 70\% of TNBCs. CERT downregulation in breast cancer cells enhanced ErbB1 lateral mobility, ligand-induced autophosphorylation, internalization, and chemotaxis. Together, our findings provide a link between lipid metabolism at the Golgi with signaling at the plasma membrane, thereby implicating CERT loss in the progression of TNBCs. %@ 4971168569301

@article{heering201210115800085472can113069, abstract = {Triple-negative breast cancers (TNBC) are especially refractory to treatment due to their negative hormone receptor and ErbB2/HER2 status. Therefore, the identification of cancer-associated deregulated signaling pathways is necessary to develop improved targeted therapies. Here, we show that expression of the ceramide transfer protein CERT is reduced in TNBCs. CERT transfers ceramide from the endoplasmic reticulum to the Golgi complex for conversion into sphingomyelin (SM). We provide evidence that by regulating cellular SM levels, CERT determines the signaling output of the EGF receptor (EGFR/ErbB1), which is upregulated in approximately 70{\%} of TNBCs. CERT downregulation in breast cancer cells enhanced ErbB1 lateral mobility, ligand-induced autophosphorylation, internalization, and chemotaxis. Together, our findings provide a link between lipid metabolism at the Golgi with signaling at the plasma membrane, thereby implicating CERT loss in the progression of TNBCs. }, added-at = {2023-06-29T13:07:55.000+0200}, author = {Heering, Johanna and Weis, Nicole and Holeiter, Monika and Neugart, Felix and Staebler, Annette and Fehm, Tanja N. and Bischoff, Annabell and Schiller, J{\"{u}}rgen and Duss, Stephan and Schmid, Simone and Korte, Thomas and Herrmann, Andreas and Olayioye, Monilola A}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/20f075bd3606dbe5dc7dc0894108819cb/fabian}, doi = {10.1158/0008-5472.CAN-11-3069}, interhash = {b0192f8ead66624216b1786eda57ac6c}, intrahash = {0f075bd3606dbe5dc7dc0894108819cb}, isbn = {4971168569301}, issn = {00085472}, journal = {Cancer Research}, keywords = {2012 izi olayioye}, month = jun, number = 11, pages = {2855--2866}, timestamp = {2023-06-29T13:07:55.000+0200}, title = {Loss of the ceramide transfer protein augments EGF receptor signaling in breast cancer}, url = {http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008-5472.CAN-11-3069}, volume = 72, year = 2012 }