dMyc functions downstream of Yorkie to promote the supercompetitive behavior of hippo pathway mutant cells.
dMyc functions downstream of Yorkie to promote the supercompetitive behavior of hippo pathway mutant cells.
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DOI：
10.1371/journal.pgen.1001140
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发表时间：
2010-09-23
期刊：
影响因子：
4.5
通讯作者：
Pession A
中科院分区：
文献类型：
--
作者：
Ziosi M;Baena-López LA;Grifoni D;Froldi F;Pession A;Garoia F;Trotta V;Bellosta P;Cavicchi S;Pession A
Genetic analyses in Drosophila epithelia have suggested that the phenomenon of “cell competition” could participate in organ homeostasis. It has been speculated that competition between different cell populations within a growing organ might play a role as either tumor promoter or tumor suppressor, depending on the cellular context. The evolutionarily conserved Hippo (Hpo) signaling pathway regulates organ size and prevents hyperplastic disease from flies to humans by restricting the activity of the transcriptional cofactor Yorkie (yki). Recent data indicate also that mutations in several Hpo pathway members provide cells with a competitive advantage by unknown mechanisms. Here we provide insight into the mechanism by which the Hpo pathway is linked to cell competition, by identifying dMyc as a target gene of the Hpo pathway, transcriptionally upregulated by the activity of Yki with different binding partners. We show that the cell-autonomous upregulation of dMyc is required for the supercompetitive behavior of Yki-expressing cells and Hpo pathway mutant cells, whereas the relative levels of dMyc between Hpo pathway mutant cells and wild-type neighboring cells are critical for determining whether cell competition promotes a tumor-suppressing or tumor-inducing behavior. All together, these data provide a paradigmatic example of cooperation between tumor suppressor genes and oncogenes in tumorigenesis and suggest a dual role for cell competition during tumor progression depending on the output of the genetic interactions occurring between confronted cells. One of the major challenges of developmental biology and cancer research is to get a better understanding of how different signals regulate proper organ growth and prevent tumor formation. Even though there is a strong correlation between tumor progression and Myc family misexpression or Hippo signaling pathway malfunction, the relationship between these organ growth regulators remains unclear. Here, we demonstrate that the Hippo signaling pathway controls the transcription of Drosophila dmyc. Furthermore, we show that the misregulated expression of dMyc in Hippo mutant cells elicits their proliferative expansion at the expense of normal surrounding cells. These findings reveal a molecular mechanism of cooperation between oncogenes and tumor suppressor genes that favors both tumor progression and wild-type tissue elimination. Additionally, our findings indicate a dual role for cell competition during the tumour progression depending on the cellular context.
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影响因子：
2.3
作者：
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通讯作者：
Quinn L
影响因子：
21.3
作者：
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通讯作者：
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作者：
Garoia, F;Grifoni, D;Cavicchi, S
通讯作者：
Cavicchi, S