Direct reprogramming by oncogenic Ras and Myc

Ischenko I.; Zhi J.; Moll U.M.Nemajerova A.Petrenko O.

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Direct reprogramming by oncogenic Ras and Myc

机译：Direct reprogramming by oncogenic Ras and Myc

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Genetically or epigenetically defined reprogramming is a hallmark of cancer cells. However, a causal association between genome reprogramming and cancer has not yet been conclusively established. In particular, little is known about the mechanisms that underlie metastasis of cancer, and even less is known about the identity of metastasizing cancer cells. In this study, we used a model of conditional expression of oncogenic KrasG12D allele in primary mouse cells to show that reprogramming and dedifferentiation is a fundamental early step in malignant transformation and cancer initiation. Our data indicate that stable expression of activated KrasG12D confers on cells a large degree of phenotypic plasticity that predisposes them to neoplastic transformation and acquisition of stem cell characteristics. We have developed a genetically tractable model system to investigate the origins and evolution of metastatic pancreatic cancer cells.We show that metastatic conversion of KrasG12D-expressing cells that exhibit different degrees of differentiation and malignancy can be reconstructed in cell culture, and that the proto-oncogene c-Myc controls the generation of self-renewing metastatic cancer cells. Collectively, our results support a model wherein non-stem cancer cells have the potential to dedifferentiate and acquire stem cell properties as a direct consequence of oncogene-induced plasticity. Moreover, the disturbance in the normally existing dynamic equilibrium between cancer stem cells and non-stem cancer cells allows the formation of cancer stem cells with high metastatic capacity at any time during cancer progression.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第10期|3937-3942|共6页
作者
Ischenko I.; Zhi J.; Moll U.M.Nemajerova A.Petrenko O.;
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Departments of Molecular Genetics and Microbiology, State University of New York, Stony Brook, NY 11794, United States;

Departments of Pathology, State University of New York, Stony Brook, NY 11794, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
中图分类自然科学总论;
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Direct reprogramming by oncogenic Ras and Myc

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