PLoS ONE (Oct 2010)

Notch signaling activation suppresses v-Src-induced transformation of neural cells by restoring TGF-β-mediated differentiation.

  • Samira Amarir,
  • Maria Marx,
  • Georges Calothy

DOI
https://doi.org/10.1371/journal.pone.0013572
Journal volume & issue
Vol. 5, no. 10
p. e13572

Abstract

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BackgroundWe have been investigating how interruption of differentiation contributes to the oncogenic process and the possibility to reverse the transformed phenotype by restoring differentiation. In a previous report, we correlated the capacity of intracellular Notch (ICN) to suppress v-Src-mediated transformation of quail neuroretina (QNR/v-src(ts)) cells with the acquisition by these undifferentiated cells of glial differentiation markers.Methodology/principal findingsIn this work, we have identified autocrine TGF-β3 signaling activation as a major effector of Notch-induced phenotypic changes, sufficient to induce transition in differentiation markers expression, suppress morphological transformation and significantly inhibit anchorage-independent growth. We also show that this signaling is constitutive of and contributes to ex-vivo autonomous QNR cell differentiation and that its down-regulation is essential to achieve v-Src-induced transformation.Conclusions/significanceThese results support the possibility that Notch signaling induces differentiation and suppresses transformation by a novel mechanism, involving secreted proteins. They also underline the importance of extracellular signals in controlling the balance between normal and transformed phenotypes.