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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
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Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency
Alba Ferreirós1, Pablo Pedrosa1, Sabela Da Silva-Álvarez1
1Laboratorio 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.
Stem Cell Reports
|May 7, 2019
Summary
Expressing the RAS oncogene aids cell reprogramming but hinders it in tumor cells. RAS promotes dedifferentiation and stemness, yet malignancy prevents complete reprogramming.
Area of Science:
- Cellular biology
- Oncology
- Stem cell research
Background:
- Cellular reprogramming can be used to study disease mechanisms.
- Cellular reprogramming and oncogenic transformation share commonalities, including cell identity changes and immortalization.
- Reprogramming tumor cells completely remains challenging.
Purpose of the Study:
- To investigate the effect of the RAS oncogene on cellular reprogramming.
- To understand how RAS influences dedifferentiation and stemness acquisition.
- To explore the barriers to reprogramming malignant cells.
Main Methods:
- Expressing reprogramming factors in somatic cells.
- Introducing the active RAS oncogene into cells.
- Analyzing gene expression changes and cell fate.
- Comparing reprogramming efficiency in normal versus neoplastic cells.
Main Results:
- Combined expression of RAS and reprogramming factors enhanced dedifferentiation.
- RAS expression within neoplastic cells impaired reprogramming.
- RAS induced paracrine expression changes promoting stemness and loss of cell identity.
- Cooperating oncogenic defects in RAS-expressing cells led to an incompatible malignant fate.
Conclusions:
- RAS can promote reprogramming by inducing dedifferentiation and stemness.
- Malignancy driven by cooperating oncogenes, including RAS, creates a cellular environment incompatible with complete reprogramming.
- Understanding these interactions is crucial for both regenerative medicine and cancer research.
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