Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling
Abstract Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by which cells survive executioner caspase activation when facing apoptotic stress. Here we demonstrate that colorectal canc...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-06-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05916-8 |
| _version_ | 1797789564728770560 |
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| author | Ru Wang Yuxing Wang Xiaohe Liu Menghao Liu Lili Sun Xiaohua Pan Huili Hu Baichun Jiang Yongxin Zou Qiao Liu Yaoqin Gong Molin Wang Gongping Sun |
| author_facet | Ru Wang Yuxing Wang Xiaohe Liu Menghao Liu Lili Sun Xiaohua Pan Huili Hu Baichun Jiang Yongxin Zou Qiao Liu Yaoqin Gong Molin Wang Gongping Sun |
| author_sort | Ru Wang |
| collection | DOAJ |
| description | Abstract Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by which cells survive executioner caspase activation when facing apoptotic stress. Here we demonstrate that colorectal cancer cells can undergo anastasis after transient exposure to chemotherapeutic drugs. Using a lineage tracing system to label and isolate cells that have experienced executioner caspase activation in response to drug treatment, we show that anastasis grants colorectal cancer cells enhanced migration, metastasis, and chemoresistance. Mechanistically, treatment with chemotherapeutic drugs induces upregulated expression of cIAP2 and activation of NFκB, which are required for cells to survive executioner caspase activation. The elevated cIAP2/NFκB signaling persists in anastatic cancer cells to promote migration and chemoresistance. Our study unveils that cIAP2/NFκB-dependent anastasis promotes acquired resistance and metastasis after chemotherapy. |
| first_indexed | 2024-03-13T01:52:27Z |
| format | Article |
| id | doaj.art-660acc5c85ea4ee9914bbdb46d99ef73 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-13T01:52:27Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-660acc5c85ea4ee9914bbdb46d99ef732023-07-02T11:28:01ZengNature Publishing GroupCell Death and Disease2041-48892023-06-0114611210.1038/s41419-023-05916-8Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signalingRu Wang0Yuxing Wang1Xiaohe Liu2Menghao Liu3Lili Sun4Xiaohua Pan5Huili Hu6Baichun Jiang7Yongxin Zou8Qiao Liu9Yaoqin Gong10Molin Wang11Gongping Sun12Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Experimental Teratology, Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityAbstract Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by which cells survive executioner caspase activation when facing apoptotic stress. Here we demonstrate that colorectal cancer cells can undergo anastasis after transient exposure to chemotherapeutic drugs. Using a lineage tracing system to label and isolate cells that have experienced executioner caspase activation in response to drug treatment, we show that anastasis grants colorectal cancer cells enhanced migration, metastasis, and chemoresistance. Mechanistically, treatment with chemotherapeutic drugs induces upregulated expression of cIAP2 and activation of NFκB, which are required for cells to survive executioner caspase activation. The elevated cIAP2/NFκB signaling persists in anastatic cancer cells to promote migration and chemoresistance. Our study unveils that cIAP2/NFκB-dependent anastasis promotes acquired resistance and metastasis after chemotherapy.https://doi.org/10.1038/s41419-023-05916-8 |
| spellingShingle | Ru Wang Yuxing Wang Xiaohe Liu Menghao Liu Lili Sun Xiaohua Pan Huili Hu Baichun Jiang Yongxin Zou Qiao Liu Yaoqin Gong Molin Wang Gongping Sun Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling Cell Death and Disease |
| title | Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling |
| title_full | Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling |
| title_fullStr | Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling |
| title_full_unstemmed | Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling |
| title_short | Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling |
| title_sort | anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating ciap2 nfκb signaling |
| url | https://doi.org/10.1038/s41419-023-05916-8 |
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