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Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Fagegaltier, Delphine 
Falciatori, Ilaria 
Castel, Stephane 
Perrimon, Norbert 

Abstract

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.

Description

Keywords

Hippo, Piwi, Ras, Warts, piRNA, transposon, Animals, Argonaute Proteins, Cell Line, Cell Proliferation, Cell Transformation, Neoplastic, Cells, Cultured, DNA Transposable Elements, Drosophila, Drosophila Proteins, Female, Gene Expression Regulation, Gene Silencing, Ovary, RNA, Small Interfering, Signal Transduction

Journal Title

Genes Dev

Conference Name

Journal ISSN

0890-9369
1549-5477

Volume Title

30

Publisher

Cold Spring Harbor Laboratory
Sponsorship
Cancer Research UK (C14303/A17197)
Cancer Research UK (21143)
We thank the Cold Spring Harbor Laboratory Microscopy Shared Resources for assistance, which are funded in part by Cancer Center Support Grant 5P30CA045508. This work was supported in part by a grant from the STARR Cancer Consortium, grants from the National Institutes of Health (NIH MERIT Award, R37GM062534 to G. J.H.), and a generous gift from Kathryn W. Davis to G.J.H. N.P. and G.J.H. are or were Investigators of the Howard Hughes Medical Institute. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. Cell lines have been deposited by A.S. at the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1). G.J.H. is supported by Cancer Research UK and is a Wellcome Trust Investigator.