<div class="csl-bib-body">
<div class="csl-entry">Honeder, S. E., Tomin, T., Abbott, K., Liesinger, L., Gindlhuber, J., Schittmayer-Schantl, M., Brcic, L., Vander Heiden, M., & Birner-Grünberger, R. (2024, April 18). <i>Unveiling Lipid Hydrolase Dynamics in NSCLC: Implications for Cancer Metabolism</i> [Conference Presentation]. 9th International Graz Symposium on Lipid and Membrane Biology, Graz, Austria. http://hdl.handle.net/20.500.12708/207726</div>
</div>
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/207726
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dc.description.abstract
Lipids are crucial for maintaining membrane homeostasis and many other functions of healthy cells. Cancer and proliferating cells rely on a sufficient supply of lipids, making lipid metabolism a promising therapeutic target in cancer. Increased uptake and biosynthesis of lipids are frequently observed cancer phenotypes, and the accumulation of neutral lipids in lipid droplets has embarked as a hallmark of aggressive cancers. We aim to understand the relationship between lipid droplet accumulation and cancer by studying the role of intracellular lipid hydrolases and their influence on the metabolism of cancer cells in the context of non-small cell lung cancer (NSCLC).
Tumors and paired normal tumor-adjacent (NTA) tissue of NSCLC patients were collected and subjected to in-depth proteomics, lipidomics, and activity-based protein profiling (ABPP) by state-of-the-art mass spectrometry techniques. ABPP identified several lipid hydrolases, including monoglyceride lipase (MGL), with decreased activity in tumors (fold change > 1.5) compared to paired NTA tissue. Proteomic profiling revealed distinct differences in lung tumor protein composition, enriched in DNA replication and ribosome proteins, while PPAR-α signaling and lipid catabolic enzymes were downregulated. Lipidomic analysis displayed elevated levels of triglycerides, monoglycerides, and ceramides in tumors, further supporting perturbation in lipid hydrolysis. Collectively, these data highlight the implication of lipid hydrolysis in NSCLC through downregulated lipid catabolism pathways.
To further understand the functional consequences of lipid hydrolase modulation, we genetically manipulated a panel of NSCLC cell lines (A549, H1299, H358, H441) by deleting adipose triglyceride lipase (ATGL) or MGL. Lipase deletion led to increased LDs, altered proliferation, and metabolic changes in some NSCLC cell lines. Metabolic flux analysis unveiled a metabolic switch in lipase-deficient cell lines, which produce more glucose-derived fatty acids, irrespective of extracellular lipid availability.
Our study delves into the intricate interplay between lipid hydrolysis enzymes, NSCLC cell metabolism, and proliferation. By unraveling these mechanisms, we aim to identify novel dependencies of lung cancer cells, providing insights into the drivers of lung cancer progression. This knowledge holds the potential to uncover new therapeutic targets and personalized treatment strategies for NSCLC.
en
dc.description.sponsorship
FWF - Österr. Wissenschaftsfonds
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dc.language.iso
en
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dc.subject
lung cancer
en
dc.subject
proteomics
en
dc.subject
lipidomics
en
dc.title
Unveiling Lipid Hydrolase Dynamics in NSCLC: Implications for Cancer Metabolism
en
dc.type
Presentation
en
dc.type
Vortrag
de
dc.contributor.affiliation
Medical University of Graz, Austria
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dc.contributor.affiliation
Massachusetts Institute of Technology, United States of America (the)
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dc.relation.grantno
F 7309-B21
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dc.type.category
Conference Presentation
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tuw.publication.invited
invited
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tuw.project.title
Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten
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tuw.researchinfrastructure
Cell Culture Core Facility (CCCF)
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tuw.researchTopic.id
M6
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tuw.researchTopic.name
Biological and Bioactive Materials
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tuw.researchTopic.value
100
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tuw.publication.orgunit
E164-01-3 - Forschungsgruppe Bioanalytik
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tuw.author.orcid
0000-0002-7071-2316
-
tuw.author.orcid
0000-0002-6166-704X
-
tuw.author.orcid
0000-0002-6155-5208
-
tuw.author.orcid
0000-0003-3249-655X
-
tuw.author.orcid
0000-0002-9098-8416
-
tuw.author.orcid
0000-0002-6702-4192
-
tuw.author.orcid
0000-0003-3950-0312
-
tuw.event.name
9th International Graz Symposium on Lipid and Membrane Biology
en
tuw.event.startdate
18-04-2024
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tuw.event.enddate
20-04-2024
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tuw.event.online
On Site
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tuw.event.type
Event for scientific audience
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tuw.event.place
Graz
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tuw.event.country
AT
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tuw.event.institution
SFB Lipid hydrolysis
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tuw.event.presenter
Honeder, Sophie Elisabeth
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tuw.event.track
Single Track
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wb.sciencebranch
Chemie
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wb.sciencebranch
Biologie
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wb.sciencebranch
Anatomie, Pathologie, Physiologie
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wb.sciencebranch.oefos
1040
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wb.sciencebranch.oefos
1060
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wb.sciencebranch.oefos
3011
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wb.sciencebranch.value
50
-
wb.sciencebranch.value
30
-
wb.sciencebranch.value
20
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item.languageiso639-1
en
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item.cerifentitytype
Publications
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item.openairecristype
http://purl.org/coar/resource_type/c_18cp
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item.openairetype
conference paper not in proceedings
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item.grantfulltext
none
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item.fulltext
no Fulltext
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crisitem.project.funder
FWF - Österr. Wissenschaftsfonds
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crisitem.project.grantno
F 7309-B21
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
Medical University of Graz
-
crisitem.author.dept
Massachusetts Institute of Technology
-
crisitem.author.dept
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.orcid
0000-0002-7071-2316
-
crisitem.author.orcid
0000-0002-6166-704X
-
crisitem.author.orcid
0000-0002-6155-5208
-
crisitem.author.orcid
0000-0003-3249-655X
-
crisitem.author.orcid
0000-0002-9098-8416
-
crisitem.author.orcid
0000-0002-6702-4192
-
crisitem.author.orcid
0000-0003-3950-0312
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164 - Institut für Chemische Technologien und Analytik
