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

• Main Authors: Samira Amarir, Maria Marx, Georges Calothy
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-10-01
• Series: PLoS ONE
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21042581/?tool=EBI

<h4>Background</h4>We 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.<h4>Methodology/principal findings</h4>In 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.<h4>Conclusions/significance</h4>These 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.