Honeder, Sophie

Liesinger, Laura

Gindlhuber, Juergen

Tomin, Tamara

Schittmayer-Schantl, Matthias

Brcic, Luka

Lindenmann, Joerg

Birner-Grünberger, Ruth

2023-09-05T07:25:29Z

2023-09-05T07:25:29Z

2023-07-30

<div class="csl-bib-body"> <div class="csl-entry">Honeder, S., Liesinger, L., Gindlhuber, J., Tomin, T., Schittmayer-Schantl, M., Brcic, L., Lindenmann, J., &#38; Birner-Grünberger, R. (2023, July 30). <i>Activity-based proteomic profiling reveals reduction of lipid hydrolase activity levels in lung tumors</i> [Poster Presentation]. FEBS 2023 Advanced Course: 15th European Summer School Advanced Proteomics, Brixen, Italy. http://hdl.handle.net/20.500.12708/188135</div> </div>

http://hdl.handle.net/20.500.12708/188135

Lipids are crucial for maintaining membrane homeostasis and many other functions of healthy cells. A sufficient supply of lipids is essential for rapidly proliferating cells. Cancer cells frequently show increased uptake of lipids, making lipid metabolism a promising therapeutic target in cancer. More recently, the accumulation of neutral lipids like triacylglycerol and cholesterol esters in lipid droplets has evolved as a hallmark of aggressive cancers. In addition to increased uptake and biosynthesis of lipids, a decrease in intracellular lipid hydrolysis contributes to lipid droplet accumulation. However, lipid hydrolases' role in the cancer context is less widely explored. By employing state-of-the-art mass spectrometry techniques, we aimed to explore lipid hydrolysis in non-small cell lung cancer (NSCLC) on the proteome, lipidome, and serine hydrolase activity level. Tumors and normal tumor-adjacent (NTA) tissue of NSCLC patients were collected and subjected to in-depth proteomics, lipidomics, and activity-based proteomic profiling (ABPP). Tissues were collected immediately after tumor resection and flash-frozen. In the case of ABPP, tissues were immediately incubated with a small serine hydrolase-specific probe recognized by active serine hydrolases. Labeling active serine hydrolases with the probe allowed us to enrich active enzymes belonging to this class of enzymes (including lipases) and subsequently quantify the abundance of active enzymes. Through ABPP, we identified several serine hydrolases with higher activities (fold change > 1.5) in healthy tissue, including monoglyceride lipase (MGL), neuropathy target esterase (PNPLA6), epoxide hydrolase (EPHX1), neutral cholesterol ester hydrolase (NCEH1) and liver carboxylesterase 1 (CES1). Proteomics analysis revealed that several of those lipid hydrolases, as well as several fatty acid-binding proteins, are also higher in abundance in NTA tissue. Furthermore, lipidomics analysis on the same tissues exposed significant triglyceride accumulation and higher levels of ceramides and lysophosphatidylcholines in tumors. Collectively, these data highlight the implication of lipid hydrolysis in NSCLC and suggest that lung cancer cells shut down lipid catabolism pathways contributing to the observed changes in the lipidome.

FWF Fonds zur Förderung der wissenschaftlichen Forschung (FWF)

en

lung cancer

activity-based proteomics

lipidomics

Activity-based proteomic profiling reveals reduction of lipid hydrolase activity levels in lung tumors

Presentation

Vortrag

Medical University of Graz, Austria

Medical University of Graz, Austria

Medical University of Graz, Austria

Medical University of Graz, Austria

F 7309-B21

Poster Presentation

Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten

M6

Biological and Bioactive Materials

100

E164-01-3 - Forschungsgruppe Bioanalytik

0000-0002-7201-6293

0000-0002-6155-5208

0000-0002-7071-2316

0000-0002-9098-8416

0000-0003-1276-7666

0000-0003-3950-0312

FEBS 2023 Advanced Course: 15th European Summer School Advanced Proteomics

FWF

W1226

30-07-2023

05-08-2023

On Site

Event for scientific audience

Brixen

IT

Honeder, Sophie

Single Track

Chemie

Pharmazie, Pharmakologie, Toxikologie

Anatomie, Pathologie, Physiologie

1040

3012

3011

50

20

30

en

conference poster not in proceedings

restricted

no Fulltext

Publications

http://purl.org/coar/resource_type/c_18co

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01-3 - Forschungsgruppe Bioanalytik

Medical University of Graz

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01-3 - Forschungsgruppe Bioanalytik

Medical University of Graz

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

0000-0002-6155-5208

0000-0002-7071-2316

0000-0003-3249-655X

0000-0002-9098-8416

0000-0003-1276-7666

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 - Institut für Chemische Technologien und Analytik

FWF - Österr. Wissenschaftsfonds

F 7309-B21