Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 384, Issue 4, pp 363–372

NME genes in epithelial morphogenesis


DOI: 10.1007/s00210-011-0607-0

Cite this article as:
Hsu, T. Naunyn-Schmiedeberg's Arch Pharmacol (2011) 384: 363. doi:10.1007/s00210-011-0607-0


The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications.


NME genesAwdDrosophilaEpithelial morphogenesisFollicle cellTrachea

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of MedicineBoston University School of MedicineBostonUSA