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Targeting MYC induc...
Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma
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- Sainero-Alcolado, Lourdes (författare)
- Karolinska Institutet,Karolinska Institute,Department of Microbiology, Tumor and Cell Biology, Biomedicum B7, Karolinska Institutet, Stockholm 17165, Sweden
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- Garde-Lapido, Elisa (författare)
- Karolinska Institutet,Karolinska Institute,Department of Microbiology, Tumor and Cell Biology, Biomedicum B7, Karolinska Institutet, Stockholm 17165, Sweden
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- Snaebjörnsson, Marteinn Thor (författare)
- Division of Tumor Metabolism and Microenvironment, German Cancer Research Center, Heidelberg 69120, Germany
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- Schoch, Sarah (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Njurcancergruppen,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Kidney cancer research group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22100, Sweden
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- Stevens, Irene (författare)
- Karolinska Institutet,Karolinska Institute,Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17165, Sweden
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- Ruiz-Pérez, María Victoria (författare)
- Karolinska Institute,Department of Microbiology, Tumor and Cell Biology, Biomedicum B7, Karolinska Institutet, Stockholm 17165, Sweden
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- Dyrager, Christine (författare)
- Uppsala universitet,Uppsala University,Organisk kemi
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- Pelechano, Vicent (författare)
- Karolinska Institutet,Karolinska Institute,Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17165, Sweden
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- Axelson, Håkan (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Njurcancergruppen,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Kidney cancer research group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22100, Sweden
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- Schulze, Almut (författare)
- Division of Tumor Metabolism and Microenvironment, German Cancer Research Center, Heidelberg 69120, Germany
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- Arsenian-Henriksson, Marie (författare)
- Karolinska Institutet,Karolinska Institute,Department of Microbiology, Tumor and Cell Biology, Biomedicum B7, Karolinska Institutet, Stockholm 17165, Sweden
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(creator_code:org_t)
- Proceedings of the National Academy of Sciences (PNAS), 2024
- 2024
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 121:7, s. 2310479121-2310479121
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- clear cell renal cell carcinoma
- glutamine
- HILPDA
- lipid droplets
- MYC
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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