Ceramide launches an acute anti-adhesion pro-migration cell signaling program in response to chemotherapy.

ABSTRACT: Chemotherapy has been reported to upregulate sphingomylinases and increase cellular ceramide, often linked to the induction to cell death. In this work, we show that sublethal doses of doxorubicin and vorinostat still increased cellular ceramide, which was located predominantly at the plasma membrane. To interrogate possible functions of this specific pool of ceramide, we used recombinant enzymes to mimic physiological levels of ceramide at the plasma membrane upon chemotherapy treatment. Using mass spectrometry and network analysis, followed by experimental confirmation, the results revealed that this pool of ceramide acutely regulates cell adhesion and cell migration pathways with weak connections to commonly established ceramide functions (eg, cell death). Neutral sphingomyelinase 2 (nS

SUBMITTER: Canals D 

PROVIDER: S-EPMC8265206 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature