Modulation of cellular migration and survival by c-Myc through the downregulation of urokinase (uPA) and uPA receptor.

Molecular and Cellular Biology
Daniela AlfanoIngram Iaccarino

Abstract

It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. ...Continue Reading

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Citations

Sep 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Gero DooseIngram Iaccarino
Feb 15, 2011·Human Pathology·Hua-chuan ZhengYasuo Takano
May 7, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sarika DaripallyVidudala V T S Prasad
Feb 12, 2014·Journal of Hepatology·Jens U MarquardtSnorri S Thorgeirsson
Mar 9, 2018·Cell Death & Disease·Francesca RicciardielloFerdinando Chiaradonna
Aug 6, 2019·International Journal of Cancer. Journal International Du Cancer·Anna De VincenzoMaria Patrizia Stoppelli
Jul 15, 2017·International Journal of Molecular Sciences·Ingram Iaccarino
Nov 3, 2020·Frontiers in Oncology·Kaifee Arman, Tarik Möröy

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