Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome
Abstract Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorl...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45493-8 |
| _version_ | 1797273986886795264 |
|---|---|
| author | Jun Xu Ying Liu Fangying Yang Yurou Cao Weihang Chen Joshua Shing Shun Li Shuai Zhang Aram Comjean Yanhui Hu Norbert Perrimon |
| author_facet | Jun Xu Ying Liu Fangying Yang Yurou Cao Weihang Chen Joshua Shing Shun Li Shuai Zhang Aram Comjean Yanhui Hu Norbert Perrimon |
| author_sort | Jun Xu |
| collection | DOAJ |
| description | Abstract Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorly understood. Recent studies in the fly uncovered that tumor secreted factors target host organs, leading to pathological effects. In this study, using a Drosophila gut tumor model, we characterize a mechanism of tumor-induced kidney dysfunction. Specifically, we find that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes. Our study describes an important mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes. |
| first_indexed | 2024-03-07T14:51:59Z |
| format | Article |
| id | doaj.art-d214a6c54ab1422f82293ce2c5d9060d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:59Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d214a6c54ab1422f82293ce2c5d9060d2024-03-05T19:41:01ZengNature PortfolioNature Communications2041-17232024-02-0115111410.1038/s41467-024-45493-8Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndromeJun Xu0Ying Liu1Fangying Yang2Yurou Cao3Weihang Chen4Joshua Shing Shun Li5Shuai Zhang6Aram Comjean7Yanhui Hu8Norbert Perrimon9CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of SciencesDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolCAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of SciencesCAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of SciencesDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolCAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of SciencesDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolDepartment of Genetics, Blavatnik Institute, Harvard Medical SchoolAbstract Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorly understood. Recent studies in the fly uncovered that tumor secreted factors target host organs, leading to pathological effects. In this study, using a Drosophila gut tumor model, we characterize a mechanism of tumor-induced kidney dysfunction. Specifically, we find that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes. Our study describes an important mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes.https://doi.org/10.1038/s41467-024-45493-8 |
| spellingShingle | Jun Xu Ying Liu Fangying Yang Yurou Cao Weihang Chen Joshua Shing Shun Li Shuai Zhang Aram Comjean Yanhui Hu Norbert Perrimon Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome Nature Communications |
| title | Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome |
| title_full | Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome |
| title_fullStr | Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome |
| title_full_unstemmed | Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome |
| title_short | Mechanistic characterization of a Drosophila model of paraneoplastic nephrotic syndrome |
| title_sort | mechanistic characterization of a drosophila model of paraneoplastic nephrotic syndrome |
| url | https://doi.org/10.1038/s41467-024-45493-8 |
| work_keys_str_mv | AT junxu mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT yingliu mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT fangyingyang mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT yuroucao mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT weihangchen mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT joshuashingshunli mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT shuaizhang mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT aramcomjean mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT yanhuihu mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome AT norbertperrimon mechanisticcharacterizationofadrosophilamodelofparaneoplasticnephroticsyndrome |