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World J Gastroenterol. Dec 14, 2014; 20(46): 17376-17387
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17376
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17376
Pea3 expression promotes the invasive and metastatic potential of colorectal carcinoma
Aruz Mesci, Stanley K Liu, Faculty of Medicine, University of Toronto, Toronto M5S 1A8, Canada
Aruz Mesci, Samira Taeb, Xiaoyong Huang, Rishi Jairath, Darshan Sivaloganathan, Stanley K Liu, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto M4N 3M5, Canada
Stanley K Liu, Department of Medical Biophysics, University of Toronto, Toronto M4N 3M5, Canada
Stanley K Liu, Department of Radiation Oncology, University of Toronto, Toronto M5S 3E2, Canada
Author contributions: Liu SK and Mesci A designed the experiments and wrote the manuscript; Mesci A, Taeb S and Huang X performed the experiments; Jairath R and Sivaloganathan S provided technical assistance.
Supported by Early investigator award to Liu SK from the Ontario Institute for Cancer Research; and the Canada Foundation for Innovation - MEDI ORF
Correspondence to: Stanley K Liu, PhD, MD, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, 2075 Bayview Avenue, Rm T2-14, Toronto, Ontario M4N 3M5, Canada. stanley.liu@sunnybrook.ca
Telephone: +1-416-4804998 Fax: +1-416-4806002
Received: March 30, 2014
Revised: June 5, 2014
Accepted: July 22, 2014
Published online: December 14, 2014
Revised: June 5, 2014
Accepted: July 22, 2014
Published online: December 14, 2014
Core Tip
Core tip: Colorectal carcinoma (CRC) is one of the leading causes of cancer mortality. Pea3 is a transcription factor that has been implicated in the pathogenesis of CRC. We demonstrate that Pea3 directly influences metastatic potential in CRC using a model of liver metastases. We provide supporting findings that CRC invasiveness, anoikis and matrix metalloproteinase activity are influenced by Pea3, and that this may collectively contribute to altered metastatic potential. Our research provides an important biological rationale to explain previously reported clinical findings that elevated Pea3 expression in human tumors is correlated with increased metastatic potential and decreased overall survival.