Abstract
Elucidating signaling events between tumor cells and their microenvironment is a major challenge in understanding cancer development. Drosophila melanogaster has emerged as an important tool for dissecting the genetic circuits tumors depend on because their imaginal discs, simple epithelia present in the larva, can be genetically manipulated to serve as models to study cancer mechanisms. Imaginal disc cells mutant for the tumor-suppressor gene scribble (scrib) lose apical-basal polarity and have the potential to form large neoplastic tumors. Interestingly, when scrib mutant (scrib−) cells are surrounded by normal cells the scrib− population is eliminated. However, the signals and mechanisms that cause the elimination of clones of scrib− cells are poorly understood. Here, we analyzed the role of Stat, a component of the JAK/STAT signaling pathway, in tissues with clones of scrib− cells. We found that Stat activity is required in normal cells for the elimination of neighboring scrib− cells. Importantly, these competitive defects of stat mutant cells are not simply due to defects in cell proliferation because even stat− cells manipulated to hyperproliferate are unable to eliminate scrib− cells. These data identify Stat activity as a critical determinant of whether or not a tissue can eliminate abnormal cells and provide an important step forward in understanding the complex network of signals operating in and around tumorigenic cells.
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Acknowledgements
We thank Erika Bach, Hugo Bellen, Andreas Bergmann, David Bilder, Michael Galko, Robert Holmgren, Kenneth Irvine, Jin Jiang, Ed Laufer, Graeme Mardon, Sang-Chul Nam, Duojia Pan, Hong Wen and the Developmental Studies Hybridoma Bank (University of Iowa) for fly stocks and antibodies. We thank Leisa McCord for artwork and the Halder lab for discussions. This work was supported by an NIH grant to GH and a Baylor Research Advocates for Student Scientists scholarship to MCS.
Author contributions: MCS, C-LC, and GH conceived the project and designed the research. MCS, C-LC, and KG performed the experiments and data analysis. MCS, C-LC, and GH wrote the paper.
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Schroeder, M., Chen, CL., Gajewski, K. et al. A non-cell-autonomous tumor suppressor role for Stat in eliminating oncogenic scribble cells. Oncogene 32, 4471–4479 (2013). https://doi.org/10.1038/onc.2012.476
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DOI: https://doi.org/10.1038/onc.2012.476
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