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.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.This is the final version of the article. It first appeared from Cold Spring Harbor Press at http://dx.doi.org/10.1101/gad.284927.116
