Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin
Abstract Understanding mechanisms of cancer cell death and the resulting effect on disease progression is crucial in cancer biology and the insight will likely offer better options for therapeutic treatment. Nuclear expulsion occurs in apoptotic cancer cells in a peptidylarginine deiminase 4 (Padi4)...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11807-z |
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| author | Justin M. Gray Woo Yong Park Ronald J. Holewinski Thorkell Andresson Carmelo Carmona-Rivera Mariana J. Kaplan Li Yang |
| author_facet | Justin M. Gray Woo Yong Park Ronald J. Holewinski Thorkell Andresson Carmelo Carmona-Rivera Mariana J. Kaplan Li Yang |
| author_sort | Justin M. Gray |
| collection | DOAJ |
| description | Abstract Understanding mechanisms of cancer cell death and the resulting effect on disease progression is crucial in cancer biology and the insight will likely offer better options for therapeutic treatment. Nuclear expulsion occurs in apoptotic cancer cells in a peptidylarginine deiminase 4 (Padi4) dependent manner. The resulting tumor cell nuclear expulsion product (TuNEP) promotes the outgrowth of neighboring cancer cells through chromatin-bound protein complexes. It is not clear what the protein compositions and functionalities are in these TuNEPs. In this study, we performed extensive proteomic profiling and identified key TuNEP protein components from mouse and human breast cancer cells as well as human lung cancer cells (4T1, MDA-MB-231, and PC9). We further compared TuNEP- specific proteins with those from apoptotic bodies or NETs from neutrophils. We found an enrichment of cellular adhesion molecules as well as increased citrullination of proteins associated with RNA binding. We showed that cellular adhesion molecules integrin and basigin (BSG) promote the growth of tumor spheroids. Our work revealed the unique TuNEP protein components distinct from neutrophil-derived NETs and shed light on potential mechanisms by which these cancer cell-derived TuNEPs promote tumor progression. |
| format | Article |
| id | doaj-art-9121c1d45b0345cfb49febedf3d1d2f3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-9121c1d45b0345cfb49febedf3d1d2f32025-08-20T03:45:52ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-11807-zProteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatinJustin M. Gray0Woo Yong Park1Ronald J. Holewinski2Thorkell Andresson3Carmelo Carmona-Rivera4Mariana J. Kaplan5Li Yang6Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of HealthLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of HealthProtein Mass Spectrometry Group, Center for Cancer Research, National Cancer Institute, National Institutes of HealthProtein Mass Spectrometry Group, Center for Cancer Research, National Cancer Institute, National Institutes of HealthSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthSystemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of HealthAbstract Understanding mechanisms of cancer cell death and the resulting effect on disease progression is crucial in cancer biology and the insight will likely offer better options for therapeutic treatment. Nuclear expulsion occurs in apoptotic cancer cells in a peptidylarginine deiminase 4 (Padi4) dependent manner. The resulting tumor cell nuclear expulsion product (TuNEP) promotes the outgrowth of neighboring cancer cells through chromatin-bound protein complexes. It is not clear what the protein compositions and functionalities are in these TuNEPs. In this study, we performed extensive proteomic profiling and identified key TuNEP protein components from mouse and human breast cancer cells as well as human lung cancer cells (4T1, MDA-MB-231, and PC9). We further compared TuNEP- specific proteins with those from apoptotic bodies or NETs from neutrophils. We found an enrichment of cellular adhesion molecules as well as increased citrullination of proteins associated with RNA binding. We showed that cellular adhesion molecules integrin and basigin (BSG) promote the growth of tumor spheroids. Our work revealed the unique TuNEP protein components distinct from neutrophil-derived NETs and shed light on potential mechanisms by which these cancer cell-derived TuNEPs promote tumor progression.https://doi.org/10.1038/s41598-025-11807-zCancerApoptosisChromatinProteomicsNuclear expulsion |
| spellingShingle | Justin M. Gray Woo Yong Park Ronald J. Holewinski Thorkell Andresson Carmelo Carmona-Rivera Mariana J. Kaplan Li Yang Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin Scientific Reports Cancer Apoptosis Chromatin Proteomics Nuclear expulsion |
| title | Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin |
| title_full | Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin |
| title_fullStr | Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin |
| title_full_unstemmed | Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin |
| title_short | Proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and RNA binding programs in extracellular chromatin |
| title_sort | proteomic analysis of tumor cell nuclear expulsion reveals significant cell adhesion and rna binding programs in extracellular chromatin |
| topic | Cancer Apoptosis Chromatin Proteomics Nuclear expulsion |
| url | https://doi.org/10.1038/s41598-025-11807-z |
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