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Muzzopappa, M., Murcia, L., Milán, M. (2017). Feedback amplification loop drives malignant growth in epithelial tissues.  Proc. Natl. Acad. Sci. U.S.A. 114(35): E7291--EE7300.
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Research paper

Interactions between cells bearing oncogenic mutations and the surrounding microenvironment, and cooperation between clonally distinct cell populations, can contribute to the growth and malignancy of epithelial tumors. The genetic techniques available in Drosophila have contributed to identify important roles of the TNF-α ligand Eiger and mitogenic molecules in mediating these interactions during the early steps of tumor formation. Here we unravel the existence of a tumor-intrinsic-and microenvironment-independent-self-reinforcement mechanism that drives tumor initiation and growth in an Eiger-independent manner. This mechanism relies on cell interactions between two functionally distinct cell populations, and we present evidence that these cell populations are not necessarily genetically different. Tumor-specific and cell-autonomous activation of the tumorigenic JNK stress-activated pathway drives the expression of secreted signaling molecules and growth factors to delaminating cells, which nonautonomously promote proliferative growth of the partially transformed epithelial tissue. We present evidence that cross-feeding interactions between delaminating and nondelaminating cells increase each other's sizes and that these interactions can explain the unlimited growth potential of these tumors. Our results will open avenues toward our molecular understanding of those social cell interactions with a relevant function in tumor initiation in humans.

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PubMed Central ID
PMC5584413 (PMC) (EuropePMC)
Related Publication(s)

Epithelial tumors: Growing from within.
Muzzopappa and Milán, 2018, Fly 12(2): 127--132 [FBrf0240048]

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    Proc. Natl. Acad. Sci. U.S.A.
    Proceedings of the National Academy of Sciences of the United States of America
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    Alleles (35)
    Genes (30)
    Human Disease Models (4)
    Natural transposons (1)
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    Transgenic Constructs (28)