CRISPR –Cas9 screening identifies the role of FER as a tumor suppressor
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| Format: | Artículo Open Access |
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Wiley
2024
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| author | Jiaqi Wang Ran Yang Fengsheng Wang Junlei Zhang Yutong Dong Jiangjun Wang Meng Yu Yixiao Xu Lianlian Liu Yuda Cheng Chen Zhang Yi Yang Wubin Yang Jiali Wang Guangxing Chen Yi Huang Yanping Tian Rui Jian Bing Ni Wei Wu Yan Ruan |
| author_facet | Jiaqi Wang Ran Yang Fengsheng Wang Junlei Zhang Yutong Dong Jiangjun Wang Meng Yu Yixiao Xu Lianlian Liu Yuda Cheng Chen Zhang Yi Yang Wubin Yang Jiali Wang Guangxing Chen Yi Huang Yanping Tian Rui Jian Bing Ni Wei Wu Yan Ruan Jiaqi Wang Ran Yang Fengsheng Wang Junlei Zhang Yutong Dong Jiangjun Wang Meng Yu Yixiao Xu Lianlian Liu Yuda Cheng Chen Zhang Yi Yang Wubin Yang Jiali Wang Guangxing Chen Yi Huang Yanping Tian Rui Jian Bing Ni Wei Wu Yan Ruan |
| collection | Wiley Open Access |
| contents | CRISPR –Cas9 screening identifies the role of FER as a tumor suppressor Jiaqi Wang Ran Yang Fengsheng Wang Junlei Zhang Yutong Dong Jiangjun Wang Meng Yu Yixiao Xu Lianlian Liu Yuda Cheng Chen Zhang Yi Yang Wubin Yang Jiali Wang Guangxing Chen Yi Huang Yanping Tian Rui Jian Bing Ni Wei Wu Yan Ruan The Journal of Pathology Abstract It is important to systematically identify tumor suppressor genes (TSGs) to improve our understanding of tumorigenesis and develop strategies for early diagnosis and mitigating disease progression. In the present study, we used an in vivo genome‐wide clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR‐associated protein 9 (Cas9) screen and identified FPS/FES‐related ( FER ) as a TSG. Single‐cell RNA sequencing (scRNA‐seq) revealed that normal cells with low FER expression exhibited elevated malignant transformation potential and stemness properties. FER knockout promoted the tumorigenic transformation, characterized by high colony‐forming efficiency and suspension growth ability, acquired tumorigenicity in vivo , increased metabolic activity, dedifferentiation properties, and immune evasion. Moreover, analysis revealed that low FER expression tumors share molecular phenotypes with FER knockout cells, suggesting the consistent role of FER in tumor initiation and progression. Taken together, our findings not only provide insights into the essential role of FER as a tumor suppressor in tumor initiation and progression but also highlight its potential as a target for future clinical diagnosis. © 2024 The Pathological Society of Great Britain and Ireland. 10.1002/path.6374 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/path.6374 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6374 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | CRISPR –Cas9 screening identifies the role of FER as a tumor suppressor Jiaqi Wang Ran Yang Fengsheng Wang Junlei Zhang Yutong Dong Jiangjun Wang Meng Yu Yixiao Xu Lianlian Liu Yuda Cheng Chen Zhang Yi Yang Wubin Yang Jiali Wang Guangxing Chen Yi Huang Yanping Tian Rui Jian Bing Ni Wei Wu Yan Ruan The Journal of Pathology CRISPR –Cas9 screening identifies the role of FER as a tumor suppressor Jiaqi Wang Ran Yang Fengsheng Wang Junlei Zhang Yutong Dong Jiangjun Wang Meng Yu Yixiao Xu Lianlian Liu Yuda Cheng Chen Zhang Yi Yang Wubin Yang Jiali Wang Guangxing Chen Yi Huang Yanping Tian Rui Jian Bing Ni Wei Wu Yan Ruan The Journal of Pathology Abstract It is important to systematically identify tumor suppressor genes (TSGs) to improve our understanding of tumorigenesis and develop strategies for early diagnosis and mitigating disease progression. In the present study, we used an in vivo genome‐wide clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR‐associated protein 9 (Cas9) screen and identified FPS/FES‐related ( FER ) as a TSG. Single‐cell RNA sequencing (scRNA‐seq) revealed that normal cells with low FER expression exhibited elevated malignant transformation potential and stemness properties. FER knockout promoted the tumorigenic transformation, characterized by high colony‐forming efficiency and suspension growth ability, acquired tumorigenicity in vivo , increased metabolic activity, dedifferentiation properties, and immune evasion. Moreover, analysis revealed that low FER expression tumors share molecular phenotypes with FER knockout cells, suggesting the consistent role of FER in tumor initiation and progression. Taken together, our findings not only provide insights into the essential role of FER as a tumor suppressor in tumor initiation and progression but also highlight its potential as a target for future clinical diagnosis. © 2024 The Pathological Society of Great Britain and Ireland. 10.1002/path.6374 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | CRISPR –Cas9 screening identifies the role of FER as a tumor suppressor |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6374 |