Ceramide synthases in cancer therapy and chemoresistance. (April 2019)

• Record Type: Journal Article
• Authors: Brachtendorf, Sebastian; El-Hindi, Khadija; Grösch, Sabine
• Is Part Of: Progress in lipid research. Volume 74(2019)
• Page Start: 160
• Page End: 185
• Publication Date: 2019-04
• Subjects: 5-FU 5-fluorouracil -- ABC ATP binding cassette -- ALL acute lymphoblastic leukemia -- AML acute myeloid leukemia -- Bcl2L13 Bcl2-like 13 -- C1P ceramide-1-phosphate -- Cer ceramide -- CerS ceramide synthase -- CML chronic myeloid leukemia -- CRC colorectal carcinoma -- CoA coenzyme A -- dhCer dihydroceramide -- DISC death-inducing signaling complex -- ER endoplasmic reticulum -- ex. exogenous -- FADD Fas-associated protein with death domain -- HCC hepatocellular carcinoma -- HDAC histone deacetylase -- HNSCC head and neck squamous cell carcinoma -- hTERT human telomerase reverse transcriptase -- IL-24 interleukin 24 -- IR ionizing radiation -- KM Michaelis constant -- MAM mitochondria-associated membrane -- MDR1 multidrug resistance protein 1 -- miR microRNA -- MMP matrix metalloproteinase -- mRNA messenger RNA -- mt mitochondrial -- N.i. no information -- NSCLC non-small-cell lung cancer -- PDT photodynamic therapy -- PERK protein kinase R-like endoplasmic reticulum kinase -- PP2A protein phosphatase 2A -- ROS reactive oxygen species -- S1P sphingosine-1-phosphate -- shRNA short hairpin RNA -- siRNA small interfering RNA -- TRAIL TNF-related apoptosis-inducing ligand -- UV ultraviolet -- V-ATPase vacuolar-H+-ATPase; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2019.04.002
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: Drug resistance is one major reason for failure of cancer therapy. In the past 10 years, evidence emerged showing that ceramides of specific chain length, generated by six different ceramide synthases (CerS), are deregulated in different cancer types thereby influencing chemosensitivity. In this review we sum up the cellular mechanisms regulated by CerS and the respective ceramides of specific chain length contributing to chemoresistance and how we can interfere with these mechanisms to overcome drug resistance by targeting CerS. We compile an overview of the different cellular effects influenced by CerS in dependency of the used drug and cancer type. Finally, the potential of CerS as new drug targets in chemotherapy or as biomarkers for the prediction of therapeutic response rates is discussed.