Two sides of the Myc-induced DNA damage response: from tumor suppression to tumor maintenance

Cell Division

Bruno Amati¹  Stefano Campaner² 

[1] Department of Experimental Oncology, European Institute of Oncology (IEO), at the IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy;Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan, Italy

关键词: Cell cycle;    Tumor suppression;    DNA damage response;    DNA damage;    CHK1;    ATR;    Replication stress;    Myc;   

Others  :  792690
DOI  :  10.1186/1747-1028-7-6

 received in 2012-02-19, accepted in 2012-02-28,  发布年份 2012

【 摘 要 】

Activation of oncogenes is generally associated with the induction of DNA damage response (DDR) signaling, which acts as a barrier to tumor progression. In this review we will present an overview of the DDR associated with oncogenic activation of Myc, with special focus on two opposite and paradoxical aspects of this response: (1) the role of the Myc-induced DDR in tumor suppression; (2) its role in dampening Myc-induced replication stress, thereby protecting the viability of prospective cancer cells. These opposing effects on cancer progression are controlled by two different branches of DDR signaling, respectively ATM/CHK2 and ATR/CHK1. Indeed, while ATM activity constitutes a barrier to malignant transformation, full activation of ATR and CHK1 is essential for tumor maintenance, providing important opportunities for therapeutic intervention. Thus, the Myc-induced DDR acts as a double-edged sword in tumor progression.

【 授权许可】

   
2012 Campaner and Amati; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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