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Título: | ING4 regulates a secretory phenotype in primary fibroblasts with dual effects on cell proliferation and tumor growth |
Autor: | Moreno, Alberto CSIC; Sotelo, I.; García-Sanz, Pablo CSIC; Moreno-Bueno, Gema CSIC ORCID; Palmero, Ignacio CSIC ORCID | Fecha de publicación: | 2014 | Editor: | Nature Publishing Group | Citación: | Oncogene 33815): 1945-1953 (2014) | Resumen: | ING proteins have an essential role in the control of a variety of cellular functions whose deregulation is associated with tumor formation and dissemination, such as proliferation, apoptosis, senescence or invasion. Accordingly, loss of function of ING proteins is a frequent event in many types of human tumors. In this report, we have studied the function of ING4, a member of the ING family of tumor suppressors, in the context of normal, non-transformed primary fibroblasts. We show that ING4 negatively regulates cell proliferation in this cell type. The antiproliferative action of ING4 requires its ability to recognize chromatin marks, it is p53-dependent at least in part, and it is lost in an ING4 cancer-associated mutant. Gene expression analysis shows that ING4 regulates the expression and release of soluble factors of the chemokine family. The secretory phenotype regulated by ING4 in primary fibroblasts displays a selective paracrine effect on proliferation, fostering the division of tumor cells, while inhibiting division in primary fibroblasts. Consistently, ING4-expressing fibroblasts promoted tumor growth in vivo in co-injection tumorigenesis assays. Collectively, our results show that ING4 not only can regulate the proliferation of primary non-transformed human fibroblasts, but also orchestrates a secretory phenotype in these cells that promotes tumor cell proliferation in vitro and in vivo. These findings support a critical role for ING4 expression in normal cells in the non-cell-autonomous regulation of tumor growth. | URI: | http://hdl.handle.net/10261/124309 | DOI: | 10.1038/onc.2013.145 | Identificadores: | doi: 10.1038/onc.2013.145 issn: 0950-9232 e-issn: 1476-5594 |
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