Nectin-4 regulates cellular senescence-associated enlargement of cell size
Abstract Cellular senescence is defined as irreversible growth arrest induced by various stress, such as DNA damage and oxidative stress. Senescent cells exhibit various characteristic morphological changes including enlarged morphology. In our recent study, we identified Nectin-4 to be upregulated...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48890-z |
| _version_ | 1797397996299616256 |
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| author | Ryoko Katasho Taiki Nagano Tetsushi Iwasaki Shinji Kamada |
| author_facet | Ryoko Katasho Taiki Nagano Tetsushi Iwasaki Shinji Kamada |
| author_sort | Ryoko Katasho |
| collection | DOAJ |
| description | Abstract Cellular senescence is defined as irreversible growth arrest induced by various stress, such as DNA damage and oxidative stress. Senescent cells exhibit various characteristic morphological changes including enlarged morphology. In our recent study, we identified Nectin-4 to be upregulated in cellular senescence by comparative transcriptomic analysis. However, there are few reports on the relationship between Nectin-4 and senescence. Therefore, we analyzed the function of Nectin-4 in senescence and its biological significance. When overexpressed with Nectin-4, the cells exhibited the enlarged cell morphology closely resembling senescent cells. In addition, the cell size enlargement during DNA damage-induced senescence was suppressed by knockdown of Nectin-4, while there were no significant changes in senescence induction. These results suggest that Nectin-4 is not involved in the regulation of senescence itself but contributes to the senescence-associated cell size increase. Furthermore, the Nectin-4-dependent cell size increase was found to be mediated by Src family kinase (SFK)/PI3 kinase (PI3K)/Rac1 pathway. To explore the functional consequences of cell size enlargement, we analyzed cell survival in Nectin-4-depleted senescent cells. Single-cell tracking experiments revealed that Nectin-4 knockdown induced apoptosis in senescent cells, and there is a strong positive correlation between cell size and survival rate. These results collectively indicate that Nectin-4 plays a causative role in the senescence-associated cell size enlargement via SFK/PI3K/Rac1, which can contribute to survival of senescent cells. |
| first_indexed | 2024-03-09T01:19:16Z |
| format | Article |
| id | doaj.art-29318c9ac0144953bd14b72dff83a2a5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:19:16Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-29318c9ac0144953bd14b72dff83a2a52023-12-10T12:16:04ZengNature PortfolioScientific Reports2045-23222023-12-0113111510.1038/s41598-023-48890-zNectin-4 regulates cellular senescence-associated enlargement of cell sizeRyoko Katasho0Taiki Nagano1Tetsushi Iwasaki2Shinji Kamada3Department of Biology, Graduate School of Science, Kobe UniversityBiosignal Research Center, Kobe UniversityDepartment of Biology, Graduate School of Science, Kobe UniversityDepartment of Biology, Graduate School of Science, Kobe UniversityAbstract Cellular senescence is defined as irreversible growth arrest induced by various stress, such as DNA damage and oxidative stress. Senescent cells exhibit various characteristic morphological changes including enlarged morphology. In our recent study, we identified Nectin-4 to be upregulated in cellular senescence by comparative transcriptomic analysis. However, there are few reports on the relationship between Nectin-4 and senescence. Therefore, we analyzed the function of Nectin-4 in senescence and its biological significance. When overexpressed with Nectin-4, the cells exhibited the enlarged cell morphology closely resembling senescent cells. In addition, the cell size enlargement during DNA damage-induced senescence was suppressed by knockdown of Nectin-4, while there were no significant changes in senescence induction. These results suggest that Nectin-4 is not involved in the regulation of senescence itself but contributes to the senescence-associated cell size increase. Furthermore, the Nectin-4-dependent cell size increase was found to be mediated by Src family kinase (SFK)/PI3 kinase (PI3K)/Rac1 pathway. To explore the functional consequences of cell size enlargement, we analyzed cell survival in Nectin-4-depleted senescent cells. Single-cell tracking experiments revealed that Nectin-4 knockdown induced apoptosis in senescent cells, and there is a strong positive correlation between cell size and survival rate. These results collectively indicate that Nectin-4 plays a causative role in the senescence-associated cell size enlargement via SFK/PI3K/Rac1, which can contribute to survival of senescent cells.https://doi.org/10.1038/s41598-023-48890-z |
| spellingShingle | Ryoko Katasho Taiki Nagano Tetsushi Iwasaki Shinji Kamada Nectin-4 regulates cellular senescence-associated enlargement of cell size Scientific Reports |
| title | Nectin-4 regulates cellular senescence-associated enlargement of cell size |
| title_full | Nectin-4 regulates cellular senescence-associated enlargement of cell size |
| title_fullStr | Nectin-4 regulates cellular senescence-associated enlargement of cell size |
| title_full_unstemmed | Nectin-4 regulates cellular senescence-associated enlargement of cell size |
| title_short | Nectin-4 regulates cellular senescence-associated enlargement of cell size |
| title_sort | nectin 4 regulates cellular senescence associated enlargement of cell size |
| url | https://doi.org/10.1038/s41598-023-48890-z |
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