Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 2 February 2010
Vol. 3, Issue 107, p. ec37
[DOI: 10.1126/scisignal.3107ec37]

EDITORS' CHOICE

Cancer Double Trouble

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

Wu et al. used mitotic recombination in the imaginal discs of the Drosophila eye antenna to create clones of cells expressing the oncogenic protein RasV12 or bearing a loss-of-function mutation in the gene encoding the polarity protein Scribbled (scrib). Cells in scrib clones became apoptotic. In contrast, tumors developed in discs with RasV12 clones or with scrib clones overexpressing RasV12 (RasV12scrib). Strikingly, larger and more invasive tumors developed in discs with separate RasV12 and scrib clones (RasV12//scrib) compared to those with RasV12 or RasV12scrib clones, suggesting that cooperation occurred between the clones to enhance tumorigenesis and metastasis. RasV12scrib and RasV12//scrib tumors showed increased mRNA abundance for unpaired (upd), upd2, and upd3, which encode cytokines that activate the JAK (Janus kinase)–STAT (signal transducers and activators of transcription) pathway, as well as increased activity of a gene reporter for the JAK-STAT pathway. Tumorigenesis was impaired by the expression of a dominant-negative mutant of the Upd receptor Domeless and was enhanced by the coexpression of Upd or Upd2 in RasV12 clones. Signaling through c-Jun N-terminal kinase (JNK) is increased in scrib clones, and scrib clones with an additional loss-of-function mutation in the gene encoding Hemipterous, the activator of Drosophila JNK, showed decreased JAK-STAT activity and reduced ability to promote tumorigenesis. Wounding induces JNK activity that propagates to neighboring cells, and it promoted tumor growth in RasV12-expressing wing discs. The authors proposed that both wounding and scrib cells induced JNK activity in RasV12 cells and that wounding-induced cell death and apoptosis of scrib cells triggered compensatory proliferation in RasV12 cells. Eyes containing clones with loss-of-function mutations in both Scrib and Stat were smaller than eyes with only the scrib clone, suggesting that the JAK-STAT pathway is required for compensatory proliferation in response to loss of Scribble. Thus, mutations in different cells can cooperate to promote tumorigenesis and invasion, and loss of Scribble triggers JNK signaling and compensatory proliferation in neighboring RasV12-expressing cells.

M. Wu, J. C. Pastor-Pareja, T. Xu, Interaction between RasV12 and scribbled clones induces tumour growth and invasion. Nature 463, 545–548 (2010). [PubMed]

Citation: W. Wong, Double Trouble. Sci. Signal. 3, ec37 (2010).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882