In vivo targeted and deterministic single-cell malignant transformation
Why does a normal cell possibly harboring genetic mutations in oncogene or tumor suppressor genes becomes malignant and develops a tumor is a subject of intense debate. Various theories have been proposed but their experimental test has been hampered by the unpredictable and improbable malignant transformation of single cells. Here, using an optogenetic approach we permanently turn on an oncogene (KRASG12V) in a single cell of a zebrafish brain that, only in synergy with the transient co-activation of a reprogramming factor (VENTX/NANOG/OCT4), undergoes a deterministic malignant transition and robustly and reproducibly develops within 6 days into a full-blown tumor. The controlled way in which a single cell can thus be manipulated to give rise to cancer lends support to the ‘ground state theory of cancer initiation’ through ‘short-range dispersal’ of the first malignant cells preceding tumor growth.
Authors
- Marine Delagrange (ORCID: https://orcid.org/0009-0002-6596-4268)
- Benjamin Tisserand
- Bertrand Ducos (ORCID: https://orcid.org/0000-0002-5322-1339)
- David Bensimon (ORCID: https://orcid.org/0000-0003-1971-9907)
- Pierluigi Scerbo (ORCID: https://orcid.org/0000-0002-3360-4367)
- Héloïse Debare (ORCID: https://orcid.org/0000-0002-8300-6226)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- École Normale Supérieure - PSL (FR)
- Sorbonne Université (FR)
- École Normale Supérieure (BI)
- Inova Design Solutions (United Kingdom) (GB)
- Institut de Biologie de l'École Normale Supérieure (FR)
- Laboratoire de Physique de l'Ecole Normale Supérieure (FR)
Publication Details
- Journal
- eLife
- Published
- 2025-03-25
- DOI
- https://doi.org/10.7554/elife.97650.3
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00