Impact of the sphingolipid metabolizing enzyme β-galactosylceramidase on mitochondrial sphingolipid profile and energetic metabolism in human melanoma cells
Capoferri, D.; Mignani, L.; Corli, M.; Belleri, M.; Kovilakath, A.; Cowart, L. A.; Mitola, S.; Presta, M.; Grillo, E.
Show abstract
Mitochondrial plasticity, characterized by the dynamic balance between glycolysis and oxidative phos-phorylation in response to genetic and microenvironmental changes, is a hallmark of melanoma progression. Sphingolipids play a significant role in various aspects of cancer cell biology, including metabolic reprogramming. Previous observations had shown that the lysosomal sphingolipid-metabolizing enzyme {beta}-galactosylceramidase (GALC) rewires the lipid profile of mouse melanoma cells, exerting pro-oncogenic functions, gene silencing leading to a decreased oncogenic activity in murine and human melanoma cells. Here, we have focused on the mitochondrial sphingolipid composition and energetic metabolism in GALC knockout (KO) A2058 human melanoma cells. Targeted analysis of the mitochondrial sphingolipid profile, transcriptomic data, and mitochondrial structural and functional studies indicate that GALC loss drives a sphingolipid-mediated reprogramming of mitochondrial metabolism in absence of major structural alterations, characterized by bioenergetic insufficiency possibly due to ceramide- and sphingomyelin-driven impairment of respiratory chain function. Overall, these data indicate that GALC KO leads to a sphin-golipid-driven mitochondrial metabolic suppression and may provide novel information for the development of efficacious approaches in mitochondrial targeting melanoma therapies.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Fatty acid synthesis supports tumor progression through keeping TORC1 receptive for Insulin/PI3K signaling 93%
- RET Receptor Tyrosine Kinase Promotes Breast Cancer Metastasis to the Brain and RET Inhibitors Pralsetinib and Selpercatinib Suppress Breast Cancer Brain Metastases 90%
- Loss of Fanconi anemia proteins causes a reliance on lysosomal exocytosis 89%
Similar papers in this journal
- Translational control of AMPK activity in melanoma 94%
- PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma 92%
- Stress adaptation pathways and HA-CD44 signaling maintain the survival of pancreatic cancer cells with centrosome amplification 91%
Similar papers in this journal
- Transcriptional Isoforms of NAD+ Kinase regulate oxidative stress resistance and melanoma metastasis 92%
- Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks 91%
- Epidermal Growth Factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium 91%
Similar papers in this journal
- FASN-deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress 93%
- Transcriptional co-activator regulates melanocyte differentiation and oncogenesis by integrating cAMP and MAPK/ERK pathways 92%
- P-cadherin mechanoactivates tumor- mesothelium metabolic coupling to promote ovarian cancer metastasis 92%
Similar papers in this journal
- L-Glyceraldehyde inhibits neuroblastoma cell growth via a multi-modal mechanism on metabolism and signaling 92%
- Histone deacetylase inhibitor induces acetyl-CoA depletion leading to lethal metabolic stress in RAS-pathway activated cells 91%
- Early neutrophilia marked by aerobic glycolysis sustains host metabolism and delays cancer cachexia 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.