Differential Ire1 determines loser cell fate in tumor-suppressive cell competition
Summary: Tumor-suppressive cell competition (TSCC) is a conserved surveillance mechanism in which neighboring cells actively eliminate oncogenic cells. Despite overwhelming studies showing that the unfolded protein response (UPR) is dysregulated in various tumors, it remains debatable whether the UP...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723013153 |
| _version_ | 1797448130671673344 |
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| author | Jiadong Zheng Yifan Guo Changyi Shi Shuai Yang Wenyan Xu Xianjue Ma |
| author_facet | Jiadong Zheng Yifan Guo Changyi Shi Shuai Yang Wenyan Xu Xianjue Ma |
| author_sort | Jiadong Zheng |
| collection | DOAJ |
| description | Summary: Tumor-suppressive cell competition (TSCC) is a conserved surveillance mechanism in which neighboring cells actively eliminate oncogenic cells. Despite overwhelming studies showing that the unfolded protein response (UPR) is dysregulated in various tumors, it remains debatable whether the UPR restrains or promotes tumorigenesis. Here, using Drosophila eye epithelium as a model, we uncover a surprising decisive role of the Ire1 branch of the UPR in regulating cell polarity gene scribble (scrib) loss-induced TSCC. Both mutation and hyperactivation of Ire1 accelerate elimination of scrib clones via inducing apoptosis and autophagy, respectively. Unexpectedly, relative Ire1 activity is also crucial for determining loser cell fate, as dysregulating Ire1 signaling in the surrounding healthy cells reversed the “loser” status of scrib clones by decreasing their apoptosis. Furthermore, we show that Ire1 is required for cell competition in mammalian cells. Together, these findings provide molecular insights into scrib-mediated TSCC and highlight Ire1 as a key determinant of loser cell fate. |
| first_indexed | 2024-03-09T14:06:01Z |
| format | Article |
| id | doaj.art-8e662191e6c84073a8203dac61344661 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:06:01Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8e662191e6c84073a8203dac613446612023-11-30T05:06:42ZengElsevierCell Reports2211-12472023-11-014211113303Differential Ire1 determines loser cell fate in tumor-suppressive cell competitionJiadong Zheng0Yifan Guo1Changyi Shi2Shuai Yang3Wenyan Xu4Xianjue Ma5Fudan University, Shanghai 200433, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, ChinaFudan University, Shanghai 200433, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, ChinaWestlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, ChinaKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, ChinaKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China; Corresponding authorFudan University, Shanghai 200433, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China; Corresponding authorSummary: Tumor-suppressive cell competition (TSCC) is a conserved surveillance mechanism in which neighboring cells actively eliminate oncogenic cells. Despite overwhelming studies showing that the unfolded protein response (UPR) is dysregulated in various tumors, it remains debatable whether the UPR restrains or promotes tumorigenesis. Here, using Drosophila eye epithelium as a model, we uncover a surprising decisive role of the Ire1 branch of the UPR in regulating cell polarity gene scribble (scrib) loss-induced TSCC. Both mutation and hyperactivation of Ire1 accelerate elimination of scrib clones via inducing apoptosis and autophagy, respectively. Unexpectedly, relative Ire1 activity is also crucial for determining loser cell fate, as dysregulating Ire1 signaling in the surrounding healthy cells reversed the “loser” status of scrib clones by decreasing their apoptosis. Furthermore, we show that Ire1 is required for cell competition in mammalian cells. Together, these findings provide molecular insights into scrib-mediated TSCC and highlight Ire1 as a key determinant of loser cell fate.http://www.sciencedirect.com/science/article/pii/S2211124723013153CP: Cell biology |
| spellingShingle | Jiadong Zheng Yifan Guo Changyi Shi Shuai Yang Wenyan Xu Xianjue Ma Differential Ire1 determines loser cell fate in tumor-suppressive cell competition Cell Reports CP: Cell biology |
| title | Differential Ire1 determines loser cell fate in tumor-suppressive cell competition |
| title_full | Differential Ire1 determines loser cell fate in tumor-suppressive cell competition |
| title_fullStr | Differential Ire1 determines loser cell fate in tumor-suppressive cell competition |
| title_full_unstemmed | Differential Ire1 determines loser cell fate in tumor-suppressive cell competition |
| title_short | Differential Ire1 determines loser cell fate in tumor-suppressive cell competition |
| title_sort | differential ire1 determines loser cell fate in tumor suppressive cell competition |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723013153 |
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