Wang Yiman, Liu Ke, Zhang Yuxin, Novak Daniel, Federico Aniello, Xu Cai, Horschitz Sandra, Vierthaler Marlene, Sun Qian, Wang Nina, Poelchen Juliane, Steinfass Tamara, Hüser Laura, Mall Moritz, Umansky Viktor, Utikal Jochen
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany.
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Baden-Württemberg, Germany.
Cell Death Dis. 2025 Jul 25;16(1):563. doi: 10.1038/s41419-025-07863-y.
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.
黑色素瘤是一种侵袭性皮肤癌，由于其高致瘤性和转移能力，在晚期具有高度致死性。将癌细胞的表型从一个谱系转变为另一个谱系，即所谓的转分化过程，会导致肿瘤细胞逆转，同时其致瘤性也会大幅降低。通过异位过表达四种神经元转录因子，我们将黑色素瘤细胞转分化为表达神经元标志物并呈现神经元样形态的神经元样细胞。此外，转分化细胞在体外和体内的致瘤和转移潜力均显著降低。与亲代细胞相比，转分化细胞对放疗也更敏感。我们得出结论，将癌细胞转分化为终末分化的神经元样细胞可能代表一种治疗黑色素瘤的前瞻性新疗法。
