YB-1 drives preneoplastic progression: Insight into opportunities for cancer prevention

Alastair H. Davies and Sandra E. Dunn 1 Laboratory of Oncogenomic Research, Departments of Pediatrics and Experimental Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada Keywords: YB-1, HER2, RSK, MAPK signaling, pre-malignancy, Kinex antibody microarray Received: April 21, 2011; Accepted: May 13, 2011; Published: May 13, 2011; Correspondence: Sandra E. Dunn, e-mail: // // Abstract Surprisingly little is known about the underlying genetic events that trigger the progression of a normal cell into a cancerous cell. We recently developed a YB-1-driven model of pre-malignancy where we uncovered that the oncogene promotes genomic instability through cell cycle checkpoint slippage and centrosome amplification. In this research perspective, we describe a possible mechanism by which YB-1 instigates preneoplastic transformation. Using Kinex antibody microarrays with coverage of 800 proteins, we discovered that pre-malignant cells exhibit deregulated signal transduction along the HER2-MAPK-RSK axis. We will discuss the implications of these finding in regard to early intervention strategies.