Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion
Abstract Melanoma is an aggressive skin cancer and highly lethal at advanced stages due to its high tumorigenicity and metastatic capacity. Changing the phenotype of cancer cells from one lineage to another, a process called transdifferentiation, leads to tumor cell reversion, which goes along with...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07863-y |
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| _version_ | 1849761054149574656 |
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| author | Yiman Wang Ke Liu Yuxin Zhang Daniel Novak Aniello Federico Cai Xu Sandra Horschitz Marlene Vierthaler Qian Sun Nina Wang Juliane Poelchen Tamara Steinfass Laura Hüser Moritz Mall Viktor Umansky Jochen Utikal |
| author_facet | Yiman Wang Ke Liu Yuxin Zhang Daniel Novak Aniello Federico Cai Xu Sandra Horschitz Marlene Vierthaler Qian Sun Nina Wang Juliane Poelchen Tamara Steinfass Laura Hüser Moritz Mall Viktor Umansky Jochen Utikal |
| author_sort | Yiman Wang |
| collection | DOAJ |
| description | Abstract Melanoma is an aggressive skin cancer and highly lethal at advanced stages due to its high tumorigenicity and metastatic capacity. Changing the phenotype of cancer cells from one lineage to another, a process called transdifferentiation, leads to tumor cell reversion, which goes along with a drastic reduction of their tumorigenicity. Via ectopic overexpression of four neuronal transcription factors, we transdifferentiated melanoma cells into neuron-like cells expressing neuronal markers and showing a neuron-like morphology. Moreover, the tumorigenic and metastatic potential of transdifferentiated cells in vitro and in vivo was significantly reduced. Transdifferentiated cells were also more sensitive to radiotherapy compared with their parental counterparts. We conclude that transdifferentiation of cancer cells into terminally differentiated neuron-like cells might represent a prospective new therapeutic approach for the treatment of melanoma. |
| format | Article |
| id | doaj-art-a3d49f87252e41d294154ea7983ee81d |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-a3d49f87252e41d294154ea7983ee81d2025-08-20T03:06:09ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111210.1038/s41419-025-07863-yDirect transdifferentiation of tumorigenic melanoma cells induces tumor cell reversionYiman Wang0Ke Liu1Yuxin Zhang2Daniel Novak3Aniello Federico4Cai Xu5Sandra Horschitz6Marlene Vierthaler7Qian Sun8Nina Wang9Juliane Poelchen10Tamara Steinfass11Laura Hüser12Moritz Mall13Viktor Umansky14Jochen Utikal15Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Radiooncology/Radiobiology Department, German Cancer Research Center (DKFZ)Department of Translational Brain Research, Central Institute of Mental Health (ZI), University of Heidelberg/Medical FacultySkin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Cell Fate Engineering and Disease Modeling Group, German Cancer Research Center (DKFZ) and DKFZ-ZMBH AllianceSkin Cancer Unit, German Cancer Research Center (DKFZ)Skin Cancer Unit, German Cancer Research Center (DKFZ)Abstract Melanoma is an aggressive skin cancer and highly lethal at advanced stages due to its high tumorigenicity and metastatic capacity. Changing the phenotype of cancer cells from one lineage to another, a process called transdifferentiation, leads to tumor cell reversion, which goes along with a drastic reduction of their tumorigenicity. Via ectopic overexpression of four neuronal transcription factors, we transdifferentiated melanoma cells into neuron-like cells expressing neuronal markers and showing a neuron-like morphology. Moreover, the tumorigenic and metastatic potential of transdifferentiated cells in vitro and in vivo was significantly reduced. Transdifferentiated cells were also more sensitive to radiotherapy compared with their parental counterparts. We conclude that transdifferentiation of cancer cells into terminally differentiated neuron-like cells might represent a prospective new therapeutic approach for the treatment of melanoma.https://doi.org/10.1038/s41419-025-07863-y |
| spellingShingle | Yiman Wang Ke Liu Yuxin Zhang Daniel Novak Aniello Federico Cai Xu Sandra Horschitz Marlene Vierthaler Qian Sun Nina Wang Juliane Poelchen Tamara Steinfass Laura Hüser Moritz Mall Viktor Umansky Jochen Utikal Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion Cell Death and Disease |
| title | Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion |
| title_full | Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion |
| title_fullStr | Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion |
| title_full_unstemmed | Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion |
| title_short | Direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion |
| title_sort | direct transdifferentiation of tumorigenic melanoma cells induces tumor cell reversion |
| url | https://doi.org/10.1038/s41419-025-07863-y |
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