The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS
Summary: Intratumoral heterogeneity is common in cancer, particularly in sarcomas like undifferentiated pleomorphic sarcoma (UPS), where individual cells demonstrate a high degree of cytogenic diversity. Previous studies showed that a small subset of cells within UPS, known as the metastatic clone (...
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Elsevier
2024-07-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224014123 |
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| author | Ga I. Ban Vijitha Puviindran Yu Xiang Puvi Nadesan Jackie Tang Jianhong Ou Nicholas Guardino Makoto Nakagawa MaKenna Browne Asjah Wallace Koji Ishikawa Eijiro Shimada John T. Martin Yarui Diao David G. Kirsch Benjamin A. Alman |
| author_facet | Ga I. Ban Vijitha Puviindran Yu Xiang Puvi Nadesan Jackie Tang Jianhong Ou Nicholas Guardino Makoto Nakagawa MaKenna Browne Asjah Wallace Koji Ishikawa Eijiro Shimada John T. Martin Yarui Diao David G. Kirsch Benjamin A. Alman |
| author_sort | Ga I. Ban |
| collection | DOAJ |
| container_title | iScience |
| description | Summary: Intratumoral heterogeneity is common in cancer, particularly in sarcomas like undifferentiated pleomorphic sarcoma (UPS), where individual cells demonstrate a high degree of cytogenic diversity. Previous studies showed that a small subset of cells within UPS, known as the metastatic clone (MC), as responsible for metastasis. Using a CRISPR-based genomic screen in-vivo, we identified the COMPASS complex member Setd1a as a key regulator maintaining the metastatic phenotype of the MC in murine UPS. Depletion of Setd1a inhibited metastasis development in the MC. Transcriptome and chromatin sequencing revealed COMPASS complex target genes in UPS, such as Cxcl10, downregulated in the MC. Deleting Cxcl10 in non-MC cells increased their metastatic potential. Treating mice with human UPS xenografts with a COMPASS complex inhibitor suppressed metastasis without affecting tumor growth in the primary tumor. Our data identified an epigenetic program in a subpopulation of sarcoma cells that maintains metastatic potential. |
| format | Article |
| id | doaj-art-144907bc7fea4fa9bea54a2af2dc7bf3 |
| institution | Directory of Open Access Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-144907bc7fea4fa9bea54a2af2dc7bf32025-08-19T23:46:19ZengElsevieriScience2589-00422024-07-0127711018710.1016/j.isci.2024.110187The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPSGa I. Ban0Vijitha Puviindran1Yu Xiang2Puvi Nadesan3Jackie Tang4Jianhong Ou5Nicholas Guardino6Makoto Nakagawa7MaKenna Browne8Asjah Wallace9Koji Ishikawa10Eijiro Shimada11John T. Martin12Yarui Diao13David G. Kirsch14Benjamin A. Alman15Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Cell Biology and Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Cell Biology and Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Cell Biology and Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USADepartment of Cell Biology and Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USADepartment of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA; The Princes Margaret Cancer Centre, Department of Radiation Oncology, University Health Network and the University of Toronto, Toronto, ON, CanadaDepartment of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USA; Corresponding authorSummary: Intratumoral heterogeneity is common in cancer, particularly in sarcomas like undifferentiated pleomorphic sarcoma (UPS), where individual cells demonstrate a high degree of cytogenic diversity. Previous studies showed that a small subset of cells within UPS, known as the metastatic clone (MC), as responsible for metastasis. Using a CRISPR-based genomic screen in-vivo, we identified the COMPASS complex member Setd1a as a key regulator maintaining the metastatic phenotype of the MC in murine UPS. Depletion of Setd1a inhibited metastasis development in the MC. Transcriptome and chromatin sequencing revealed COMPASS complex target genes in UPS, such as Cxcl10, downregulated in the MC. Deleting Cxcl10 in non-MC cells increased their metastatic potential. Treating mice with human UPS xenografts with a COMPASS complex inhibitor suppressed metastasis without affecting tumor growth in the primary tumor. Our data identified an epigenetic program in a subpopulation of sarcoma cells that maintains metastatic potential.http://www.sciencedirect.com/science/article/pii/S2589004224014123EpigeneticsCancerGenomicsTranscriptomics |
| spellingShingle | Ga I. Ban Vijitha Puviindran Yu Xiang Puvi Nadesan Jackie Tang Jianhong Ou Nicholas Guardino Makoto Nakagawa MaKenna Browne Asjah Wallace Koji Ishikawa Eijiro Shimada John T. Martin Yarui Diao David G. Kirsch Benjamin A. Alman The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS Epigenetics Cancer Genomics Transcriptomics |
| title | The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS |
| title_full | The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS |
| title_fullStr | The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS |
| title_full_unstemmed | The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS |
| title_short | The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS |
| title_sort | compass complex maintains the metastatic capacity imparted by a subpopulation of cells in ups |
| topic | Epigenetics Cancer Genomics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224014123 |
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