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

作者: Daniel Canals , Silvia Salamone , Bruno Jaime Santacreu , Erika Nemeth , Daniel Aguilar

DOI: 10.1096/FJ.202000205R

关键词: Cell biologySphingolipidCell migrationDownregulation and upregulationSphingomyelinCell adhesionCeramideCell signalingChemistryProgrammed cell death

摘要: Chemotherapy has been reported to upregulate sphingomylinases and increase cellular ceramide, often linked the induction cell death. In this work, we show that sublethal doses of doxorubicin vorinostat still increased which was located predominantly at plasma membrane. To interrogate possible functions specific pool used recombinant enzymes mimic physiological levels ceramide membrane upon chemotherapy treatment. Using mass spectrometry network analysis, followed by experimental confirmation, results revealed acutely regulates adhesion migration pathways with weak connections commonly established (eg, death). Neutral sphingomyelinase 2 (nSMase2) identified as responsible for generation treatment, both nSMase2 were necessary sufficient mediate these "side" effects on migration. This is first time a interrogated acute signaling functions, define an effector regulation under chemotherapeutical stress.

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