The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma
Summary: Most cancers re-activate telomerase to maintain telomere length and thus acquire immortality. Activating telomerase promoter mutations are found in many cancers, including melanoma. However, it is unclear when and if telomerase is strictly required during tumorigenesis. We combined the telo...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472401386X |
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| author | Bruno Lopes-Bastos Joana Nabais Tânia Ferreira Giulia Allavena Mounir El Maï Malia Bird Seniye Targen Lorenzo Tattini Da Kang Jia-Xing Yue Gianni Liti Tânia G. Carvalho Miguel Godinho Ferreira |
| author_facet | Bruno Lopes-Bastos Joana Nabais Tânia Ferreira Giulia Allavena Mounir El Maï Malia Bird Seniye Targen Lorenzo Tattini Da Kang Jia-Xing Yue Gianni Liti Tânia G. Carvalho Miguel Godinho Ferreira |
| author_sort | Bruno Lopes-Bastos |
| collection | DOAJ |
| description | Summary: Most cancers re-activate telomerase to maintain telomere length and thus acquire immortality. Activating telomerase promoter mutations are found in many cancers, including melanoma. However, it is unclear when and if telomerase is strictly required during tumorigenesis. We combined the telomerase mutant (tert−/−) with two established zebrafish melanoma models. We show that tert−/− melanomas initially develop with similar incidence and invasiveness to tert+/+ tumors. However, they eventually decline in growth and regress. Late tert−/− tumors exhibit reduced cell proliferation, increased apoptosis, and melanocyte differentiation. Notably, these tumors show enhanced immune cell infiltration and can resume growth when transplanted into immunocompromised hosts. We propose that telomerase is required for melanoma in zebrafish, albeit at later stages of progression, to sustain tumor growth while avoiding immune rejection and regression. Thus, the absence of telomerase restricts melanoma through tumor-autonomous mechanisms (cell-cycle arrest, apoptosis, and melanocyte differentiation) and a non-tumor-autonomous mechanism (immune rejection). |
| format | Article |
| id | doaj-art-d79b0b93c29b415781b98225e061db8c |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-d79b0b93c29b415781b98225e061db8c2024-12-06T05:13:22ZengElsevierCell Reports2211-12472024-12-014312115035The absence of telomerase leads to immune response and tumor regression in zebrafish melanomaBruno Lopes-Bastos0Joana Nabais1Tânia Ferreira2Giulia Allavena3Mounir El Maï4Malia Bird5Seniye Targen6Lorenzo Tattini7Da Kang8Jia-Xing Yue9Gianni Liti10Tânia G. Carvalho11Miguel Godinho Ferreira12Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, France; Instituto Gulbenkian de Ciência, 2780-156 Oeiras, PortugalInstituto Gulbenkian de Ciência, 2780-156 Oeiras, PortugalInstituto Gulbenkian de Ciência, 2780-156 Oeiras, PortugalInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, FranceInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, France; Instituto Gulbenkian de Ciência, 2780-156 Oeiras, PortugalInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, FranceInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, FranceInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, FranceState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, FranceChampalimaud Center for the Unknown, 1400-038 Lisboa, PortugalInstitute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Côte d’Azur, 06107 Nice, France; Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal; Corresponding authorSummary: Most cancers re-activate telomerase to maintain telomere length and thus acquire immortality. Activating telomerase promoter mutations are found in many cancers, including melanoma. However, it is unclear when and if telomerase is strictly required during tumorigenesis. We combined the telomerase mutant (tert−/−) with two established zebrafish melanoma models. We show that tert−/− melanomas initially develop with similar incidence and invasiveness to tert+/+ tumors. However, they eventually decline in growth and regress. Late tert−/− tumors exhibit reduced cell proliferation, increased apoptosis, and melanocyte differentiation. Notably, these tumors show enhanced immune cell infiltration and can resume growth when transplanted into immunocompromised hosts. We propose that telomerase is required for melanoma in zebrafish, albeit at later stages of progression, to sustain tumor growth while avoiding immune rejection and regression. Thus, the absence of telomerase restricts melanoma through tumor-autonomous mechanisms (cell-cycle arrest, apoptosis, and melanocyte differentiation) and a non-tumor-autonomous mechanism (immune rejection).http://www.sciencedirect.com/science/article/pii/S221112472401386XCP: Cancer |
| spellingShingle | Bruno Lopes-Bastos Joana Nabais Tânia Ferreira Giulia Allavena Mounir El Maï Malia Bird Seniye Targen Lorenzo Tattini Da Kang Jia-Xing Yue Gianni Liti Tânia G. Carvalho Miguel Godinho Ferreira The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma Cell Reports CP: Cancer |
| title | The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma |
| title_full | The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma |
| title_fullStr | The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma |
| title_full_unstemmed | The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma |
| title_short | The absence of telomerase leads to immune response and tumor regression in zebrafish melanoma |
| title_sort | absence of telomerase leads to immune response and tumor regression in zebrafish melanoma |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S221112472401386X |
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