Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2
Abstract Distant metastasis is the primary cause of breast cancer-associated death. The existing information, such as the precise molecular mechanisms and effective therapeutic strategies targeting metastasis, is insufficient to combat breast cancer. This study demonstrates that the protein tyrosine...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05167-z |
| _version_ | 1811340417468203008 |
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| author | Tao Wang Xinlei Ba Xiaonan Zhang Na Zhang Guowen Wang Bin Bai Tong Li Jiahui Zhao Yanjiao Zhao Yang Yu Bing Wang |
| author_facet | Tao Wang Xinlei Ba Xiaonan Zhang Na Zhang Guowen Wang Bin Bai Tong Li Jiahui Zhao Yanjiao Zhao Yang Yu Bing Wang |
| author_sort | Tao Wang |
| collection | DOAJ |
| description | Abstract Distant metastasis is the primary cause of breast cancer-associated death. The existing information, such as the precise molecular mechanisms and effective therapeutic strategies targeting metastasis, is insufficient to combat breast cancer. This study demonstrates that the protein tyrosine phosphatase PTPN18 is downregulated in metastatic breast cancer tissues and is associated with better metastasis-free survival. Ectopic expression of PTPN18 inhibits breast cancer cell metastasis. PTPN18 is translocated from the cytoplasm to the nucleus by MVP and importin β2 in breast cancer. Then, nuclear PTPN18 dephosphorylates ETS1 and promotes its degradation. Moreover, nuclear PTPN18 but not cytoplasmic PTPN18 suppresses transforming growth factor-β signaling and epithelial-to-mesenchymal transition by targeting ETS1. Our data highlight PTPN18 as a suppressor of breast cancer metastasis and provide an effective antimetastatic therapeutic strategy. |
| first_indexed | 2024-04-13T18:41:36Z |
| format | Article |
| id | doaj.art-48606cb6be5247988d66de73d6eafee4 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T18:41:36Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-48606cb6be5247988d66de73d6eafee42022-12-22T02:34:42ZengNature Publishing GroupCell Death and Disease2041-48892022-08-0113811010.1038/s41419-022-05167-zNuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2Tao Wang0Xinlei Ba1Xiaonan Zhang2Na Zhang3Guowen Wang4Bin Bai5Tong Li6Jiahui Zhao7Yanjiao Zhao8Yang Yu9Bing Wang10College of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityDepartment of Thoracic surgery, The First Affiliated Hospital of Bengbu Medical CollegeCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityCollege of Life and Health Sciences, Northeastern UniversityAbstract Distant metastasis is the primary cause of breast cancer-associated death. The existing information, such as the precise molecular mechanisms and effective therapeutic strategies targeting metastasis, is insufficient to combat breast cancer. This study demonstrates that the protein tyrosine phosphatase PTPN18 is downregulated in metastatic breast cancer tissues and is associated with better metastasis-free survival. Ectopic expression of PTPN18 inhibits breast cancer cell metastasis. PTPN18 is translocated from the cytoplasm to the nucleus by MVP and importin β2 in breast cancer. Then, nuclear PTPN18 dephosphorylates ETS1 and promotes its degradation. Moreover, nuclear PTPN18 but not cytoplasmic PTPN18 suppresses transforming growth factor-β signaling and epithelial-to-mesenchymal transition by targeting ETS1. Our data highlight PTPN18 as a suppressor of breast cancer metastasis and provide an effective antimetastatic therapeutic strategy.https://doi.org/10.1038/s41419-022-05167-z |
| spellingShingle | Tao Wang Xinlei Ba Xiaonan Zhang Na Zhang Guowen Wang Bin Bai Tong Li Jiahui Zhao Yanjiao Zhao Yang Yu Bing Wang Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2 Cell Death and Disease |
| title | Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2 |
| title_full | Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2 |
| title_fullStr | Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2 |
| title_full_unstemmed | Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2 |
| title_short | Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2 |
| title_sort | nuclear import of ptpn18 inhibits breast cancer metastasis mediated by mvp and importin β2 |
| url | https://doi.org/10.1038/s41419-022-05167-z |
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