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Stem Cell Reports. 2019 May 14;12(5):1099-1112. doi: 10.1016/j.stemcr.2019.04.006. Epub 2019 May 2.

Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency.

Author information

1
Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706 Santiago de Compostela, Spain.
2
Histopathology Core Unit, Spanish National Cancer Research Centre (CNIO), E28029 Madrid, Spain.
3
Cellular Plasticity & Disease Modelling, Department of Developmental & Stem Cell Biology, CNRS UMR 3738 Institut Pasteur, 75015 Paris, France.
4
Departamento de Ciencias Morfológicas, Facultad de Medicina, USC, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706 Santiago de Compostela, Spain.
5
Servicio de Farmacia, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706 Santiago de Compostela, Spain.
6
Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), E15782 Santiago de Compostela, Spain. Electronic address: anxo.vidal@usc.es.
7
Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706 Santiago de Compostela, Spain. Electronic address: manuel.collado.rodriguez@sergas.es.

Abstract

Induction of pluripotency in somatic cells with defined genetic factors has been successfully used to investigate the mechanisms of disease initiation and progression. Cellular reprogramming and oncogenic transformation share common features; both involve undergoing a dramatic change in cell identity, and immortalization is a key step for cancer progression that enhances reprogramming. However, there are very few examples of complete successful reprogramming of tumor cells. Here we address the effect of expressing an active oncogene, RAS, on the process of reprogramming and found that, while combined expression with reprogramming factors enhanced dedifferentiation, expression within the context of neoplastic transformation impaired reprogramming. RAS induces expression changes that promote loss of cell identity and acquisition of stemness in a paracrine manner and these changes result in reprogramming when combined with reprogramming factors. When cells carry cooperating oncogenic defects, RAS drives cells into an incompatible cellular fate of malignancy.

KEYWORDS:

Ras; cell plasticity; cell reprogramming; iPSC; oncogenes

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