Honeder, Sophie Elisabeth

Liesinger, Laura

Hadrbolec, Matthias

Mayr, Moritz

Pirchheim, Anita

Prem, Dominik

Gindlhuber, Juergen

Brcic, Luka

Lindenmann, Joerg

Haemmerle, Guenter

Kratky, Dagmar

Schittmayer-Schantl, Matthias

Tomin, Tamara

Birner-Grünberger, Ruth

2025-10-02T08:58:38Z

2025-10-02T08:58:38Z

2025-09-23

<div class="csl-bib-body"> <div class="csl-entry">Honeder, S. E., Liesinger, L., Hadrbolec, M., Mayr, M., Pirchheim, A., Prem, D., Gindlhuber, J., Brcic, L., Lindenmann, J., Haemmerle, G., Kratky, D., Schittmayer-Schantl, M., Tomin, T., &#38; Birner-Grünberger, R. (2025, September 23). <i>Lung Tumors Exhibit Reduced Lipid Hydrolase Activity Alongside Altered Lipidome and Metabolism</i> [Conference Presentation]. ICBL 2025, Innsbruck, Austria. http://hdl.handle.net/20.500.12708/219607</div> </div>

http://hdl.handle.net/20.500.12708/219607

Alterations in lipid metabolism are a hallmark of cancer, with increased lipogenesis, fatty acid uptake, and lipid droplet accumulation emerging as defining features of many solid tumors. However, the role of lipid hydrolysis in cancer metabolism remains underexplored. To address this, we employed unbiased serine hydrolase-directed activity-based protein profiling of patient-derived lung tumors and adjacent normal tissue, combined with comprehensive proteomics and lipidomics analysis. Strikingly, several lipid hydrolases showed reduced activity and abundance in lung tumors, including monoglyceride lipase (MGL), epoxide hydrolase 1 (EPHX1), carboxylesterase 1 (CES1), neutral cholesterol ester hydrolase 1 (NCEH1), and patatin-like phospholipase domain-containing protein 6 (PNPLA6). Concomitantly, the lipid profile of tumors was altered, with many lipid species elevated compared to normal tissue. Triacylglycerols were especially enriched in tumors, particularly those containing long-chain and highly unsaturated fatty acids, suggesting lipid droplet accumulation. This was further supported by increased levels of the lipid droplet scaffolding protein Perilipin-2 (PLIN2), while ATGL - the main triacylglycerol hydrolase - was reduced in tumors, as confirmed by immunofluorescent staining. Lipid substrate assays of the downregulated hydrolases revealed that most of the lipid hydrolases reduced in lung tumors possess monoacylglycerol hydrolysis activity, amongst others. Consistent with this, several monoacylglycerol species and the overall lipid class were more abundant in tumors, corroborating decreased monoacylglycerol hydrolysis in lung tumors. To investigate the functional consequences of reduced lipid hydrolase expression, we generated NSCLC cell lines stably overexpressing ATGL, MGL, EPHX1, CES1, NCEH1, and PNPLA6. Overexpression led to reduced proliferation and, in some cases, caused a concurrent increase in fatty acid β-oxidation, a pathway found suppressed in tumor tissue. Lipidomic profiling of these cells is ongoing to identify specific lipid alterations associated with hydrolase overexpression. Together, our findings indicate that reduced lipid hydrolase activity is a feature of lung tumors that contributes to a reprogrammed lipid metabolism and altered lipid profile. This shift may support tumor growth by limiting fatty acid oxidation and associated oxidative stress.

FWF - Österr. Wissenschaftsfonds

en

lung cancer

lipid hydrolases

lipid metabolism

Lung Tumors Exhibit Reduced Lipid Hydrolase Activity Alongside Altered Lipidome and Metabolism

Presentation

Vortrag

TU Wien

Medical University of Graz, Austria

Institute of Molecular Biosciences - University of Graz (Graz, AT)

Cardiology - Medical University of Graz (Graz, AT)

Department of Pathology - Medical University of Vienna (Vienna, AT)

Gottfried Schatz Research Center - Medical University of Graz (Graz, AT)

F 7309-B21

Conference Presentation

Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten

Cell Culture Core Facility (CCCF)

X1

Beyond TUW-research focus

100

E164-01-3 - Forschungsgruppe Bioanalytik

0009-0004-6992-5770

0000-0002-6155-5208

0000-0002-9098-8416

0000-0003-1276-7666

0000-0003-1357-7573

0000-0003-3249-655X

0000-0002-7071-2316

0000-0003-3950-0312

ICBL 2025

21-09-2025

24-09-2025

On Site

Event for scientific audience

Innsbruck

AT

Honeder, Sophie Elisabeth

Single Track

Chemie

Biologie

Anatomie, Pathologie, Physiologie

1040

1060

3011

50

20

30

en

none

conference paper not in proceedings

http://purl.org/coar/resource_type/c_18cp

Publications

no Fulltext

FWF - Österr. Wissenschaftsfonds

F 7309-B21

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01-3 - Forschungsgruppe Bioanalytik

TU Wien

Medical University of Graz, Austria

Institute of Molecular Biosciences - University of Graz (Graz, AT)

Cardiology - Medical University of Graz (Graz, AT)

Department of Pathology - Medical University of Vienna (Vienna, AT)

Gottfried Schatz Research Center - Medical University of Graz (Graz, AT)

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

0009-0004-6992-5770

0000-0002-6155-5208

0000-0002-9098-8416

0000-0003-1276-7666

0000-0003-1357-7573

0000-0003-3249-655X

0000-0002-7071-2316

0000-0003-3950-0312

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164 - Institut für Chemische Technologien und Analytik