The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization
Open accessAbstract
Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used Δ9-tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms that determine the selective activation of autophagy-mediated cancer cell death.
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Citations
Cites
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“S4C), 2 proteins located in these structures.(3,33) Taken together, these observations support the conclusion that THC, but not nutrient deprivation, enhances sphingolipid biosynthesis and inhibits the transport of sphingolipids from the ER to the Golgi.”
BackgroundSelf-citationRegulation mechanisms and signaling pathways of autophagy
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Self-citationPlasma membrane contributes to the formation of pre-autophagosomal structures
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Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy
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“It is worth noting that ceramides had been previously implicated in autophagy-associated cell death via induction of lethal mitophagy.(44) However, we did not find a significant increase in mitophagy upon treatment with THC (data not shown) indicating that this mechanism is not responsible for the stimulation of autop…”
BackgroundInfluential
Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationSphingolipids and their metabolism in physiology and disease
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Sphingolipid metabolism in cancer signalling and therapy
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Epidemiology of Glioblastoma Multiforme–Literature Review
Grochans, S., Cybulska, A. M., Simińska, D., Korbecki, J., Kojder, K., Chlubek, D., & Baranowska-Bosiacka, I. (2022) · Cancers · doi:10.3390/cancers14102412 · Cited by 630
Metadata
- Authors
- Hernández-Tiedra, S., Fabriàs, G., Dávila, D., Salanueva, Í. J., Casas, J., Montes, L. R., Antón, Z., García-Taboada, E., Salazar-Roa, M., Lorente, M., Nylandsted, J., Armstrong, J., López-Valero, I., McKee, C. S., Serrano-Puebla, A., García-López, R., González-Martínez, J., Abad, J. L., Hanada, K., Boya, P., Goñi, F., Guzmán, M., Lovat, P., Jäättelä, M., Alonso, A., & Velasco, G.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-09-16
- Volume
- 12
- Issue
- 11
- Pages
- 2213-2229
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2518834230
- Cited by
- 160
- References
- 10
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Hernández-Tiedra, S., Fabriàs, G., Dávila, D., Salanueva, Í. J., Casas, J., Montes, L. R., Antón, Z., García-Taboada, E., Salazar-Roa, M., Lorente, M., Nylandsted, J., Armstrong, J., López-Valero, I., McKee, C. S., Serrano-Puebla, A., García-López, R., González-Martínez, J., Abad, J. L., Hanada, K., . . . Velasco, G. (2016). Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy. https://doi.org/10.1080/15548627.2016.1213927
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
