Effects of alpelisib treatment on murine Pten-deficient lipomas
Phosphatase and tensin homolog (PTEN) hamartoma tumour syndrome (PHTS) is a rare disorder caused by germline mutations in the tumour suppressor gene PTEN, a key negative regulator of phosphatidylinositol 3-kinase (PI3K)/AKT signalling. Children with PHTS often develop lipomas, for which only surgica...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Adipocyte |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21623945.2025.2468275 |
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| author | Lea M. Merz Karsten Winter Sandy Richter Sonja Kallendrusch Andreas Horn Sonja Grunewald Nora Klöting Kerstin Krause Wieland Kiess Diana Le Duc Antje Garten |
| author_facet | Lea M. Merz Karsten Winter Sandy Richter Sonja Kallendrusch Andreas Horn Sonja Grunewald Nora Klöting Kerstin Krause Wieland Kiess Diana Le Duc Antje Garten |
| author_sort | Lea M. Merz |
| collection | DOAJ |
| description | Phosphatase and tensin homolog (PTEN) hamartoma tumour syndrome (PHTS) is a rare disorder caused by germline mutations in the tumour suppressor gene PTEN, a key negative regulator of phosphatidylinositol 3-kinase (PI3K)/AKT signalling. Children with PHTS often develop lipomas, for which only surgical resection is available as treatment. We investigated the effects of the selective PI3K-inhibitor alpelisib on Pten-deficient lipomas. After incubation with alpelisib or the non-selective PI3K inhibitor wortmannin, we analysed histology, gene expression, and Pi3k pathway in lipoma and control epididymal adipose tissue (epiWAT). Alpelisib increased adipocyte area in lipomas compared to epiWAT. Baseline gene expression showed higher levels of markers for proliferation (Pcna), fibrosis (Tgfb1), and adipogenesis (Pparg) in lipomas, while hormone-sensitive lipase expression was lower than in epiWAT. Following alpelisib incubation, target genes of Pi3k signalling and extracellular matrix factors were reduced. We confirmed Pi3k inhibition through detecting decreased Akt levels compared to control treatment. Human lipoma samples treated with alpelisib showed variable lipolysis responses, suggesting variability in therapeutic outcomes. We established an ex vivo model to study alpelisib effects on Pten-deficient lipomas. These results underscore the therapeutic potential of targeted PI3K inhibition in the treatment of PHTS-associated lipomas, particularly in cases that are inoperable. |
| format | Article |
| id | doaj-art-111da89f7bcb42d1bac088c500e1dc4d |
| institution | DOAJ |
| issn | 2162-3945 2162-397X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Adipocyte |
| spelling | doaj-art-111da89f7bcb42d1bac088c500e1dc4d2025-08-20T03:05:21ZengTaylor & Francis GroupAdipocyte2162-39452162-397X2025-12-0114110.1080/21623945.2025.2468275Effects of alpelisib treatment on murine Pten-deficient lipomasLea M. Merz0Karsten Winter1Sandy Richter2Sonja Kallendrusch3Andreas Horn4Sonja Grunewald5Nora Klöting6Kerstin Krause7Wieland Kiess8Diana Le Duc9Antje Garten10Center for Pediatric Research, University Hospital for Children & Adolescents, Leipzig University, Leipzig, GermanyInstitute of Anatomy, Leipzig University, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children & Adolescents, Leipzig University, Leipzig, GermanyInstitute of Anatomy, Leipzig University, Leipzig, GermanyInstitute of Anatomy, Leipzig University, Leipzig, GermanyDepartment for Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich at the University and University Hospital Leipzig, Leipzig, GermanyDepartment of Endocrinology, Nephrology and Rheumatology, University Hospital Leipzig, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children & Adolescents, Leipzig University, Leipzig, GermanyInstitute of Human Genetics, University Hospital Leipzig, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children & Adolescents, Leipzig University, Leipzig, GermanyPhosphatase and tensin homolog (PTEN) hamartoma tumour syndrome (PHTS) is a rare disorder caused by germline mutations in the tumour suppressor gene PTEN, a key negative regulator of phosphatidylinositol 3-kinase (PI3K)/AKT signalling. Children with PHTS often develop lipomas, for which only surgical resection is available as treatment. We investigated the effects of the selective PI3K-inhibitor alpelisib on Pten-deficient lipomas. After incubation with alpelisib or the non-selective PI3K inhibitor wortmannin, we analysed histology, gene expression, and Pi3k pathway in lipoma and control epididymal adipose tissue (epiWAT). Alpelisib increased adipocyte area in lipomas compared to epiWAT. Baseline gene expression showed higher levels of markers for proliferation (Pcna), fibrosis (Tgfb1), and adipogenesis (Pparg) in lipomas, while hormone-sensitive lipase expression was lower than in epiWAT. Following alpelisib incubation, target genes of Pi3k signalling and extracellular matrix factors were reduced. We confirmed Pi3k inhibition through detecting decreased Akt levels compared to control treatment. Human lipoma samples treated with alpelisib showed variable lipolysis responses, suggesting variability in therapeutic outcomes. We established an ex vivo model to study alpelisib effects on Pten-deficient lipomas. These results underscore the therapeutic potential of targeted PI3K inhibition in the treatment of PHTS-associated lipomas, particularly in cases that are inoperable.https://www.tandfonline.com/doi/10.1080/21623945.2025.2468275Adipose tissuephosphatidylinositol 3-kinasephosphatase and tensin homologtissue slice culturewortmannin |
| spellingShingle | Lea M. Merz Karsten Winter Sandy Richter Sonja Kallendrusch Andreas Horn Sonja Grunewald Nora Klöting Kerstin Krause Wieland Kiess Diana Le Duc Antje Garten Effects of alpelisib treatment on murine Pten-deficient lipomas Adipocyte Adipose tissue phosphatidylinositol 3-kinase phosphatase and tensin homolog tissue slice culture wortmannin |
| title | Effects of alpelisib treatment on murine Pten-deficient lipomas |
| title_full | Effects of alpelisib treatment on murine Pten-deficient lipomas |
| title_fullStr | Effects of alpelisib treatment on murine Pten-deficient lipomas |
| title_full_unstemmed | Effects of alpelisib treatment on murine Pten-deficient lipomas |
| title_short | Effects of alpelisib treatment on murine Pten-deficient lipomas |
| title_sort | effects of alpelisib treatment on murine pten deficient lipomas |
| topic | Adipose tissue phosphatidylinositol 3-kinase phosphatase and tensin homolog tissue slice culture wortmannin |
| url | https://www.tandfonline.com/doi/10.1080/21623945.2025.2468275 |
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