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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Heering J,Weis N,Holeiter M,Neugart F,Staebler A,Fehm TN,Bischoff A,Schiller J,Duss S,Schmid S,Korte T,Herrmann A,Olayioye MAdoi
10.1158/0008-5472.CAN-11-3069subject
Has Abstractpub_date
2012-06-01 00:00:00pages
2855-66issue
11eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-3069journal_volume
72pub_type
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