期刊
GENES & DEVELOPMENT
卷 30, 期 14, 页码 1623-1635出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.284927.116
关键词
Piwi; piRNA; transposon; Ras; Warts; Hippo
资金
- Cancer Center Support Grant [5P30CA045508]
- STARR Cancer Consortium
- National Institutes of Health (NIH MERIT Award) [R37GM062534]
- Cancer Research UK
- Cancer Research UK [21143] Funding Source: researchfish
Germline genes often become re-expressed in soma-derived human cancers as cancer/testis antigens (CTAs), and piRNA (PIWI-interacting RNA) pathway proteins are found among CTAs. However, whether and how the piRNA pathway contributes to oncogenesis in human neoplasms remain poorly understood. We found that oncogenic Ras combined with loss of the Hippo tumor suppressor pathway reactivates a primary piRNA pathway in Drosophila somatic cells coincident with oncogenic transformation. In these cells, Piwi becomes loaded with piRNAs derived from annotated generative loci, which are normally restricted to either the germline or the somatic follicle cells. Negating the pathway leads to increases in the expression of a wide variety of transposons and also altered expression of some protein-coding genes. This correlates with a reduction in the proliferation of the transformed cells in culture, suggesting that, at least in this context, the piRNA pathway may play a functional role in cancer.
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