1. ¹Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA, USA
2. ²Department of Public Health Sciences, University of Virginia Health Sciences Center, Charlottesville, VA, USA
3. ³Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
4. ⁴Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA

Correspondence: Professor D Theodorescu, Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Box 422, Charlottesville, VA 22908, USA. E-mail: dt9d@virginia.edu

Received 19 May 2008; Revised 16 June 2008; Accepted 22 June 2008; Published online 25 August 2008.

Abstract

Cell migration is essential to cancer invasion and metastasis and is spatially and temporally integrated through transcriptionally dependent and independent mechanisms. As cell migration is studied in vitro, it is important to identify genes that both drive cell migration and are biologically relevant in promoting invasion and metastasis in patients with cancer. Here, gene expression profiling and a high-throughput cell migration system answers this question in human bladder cancer. In vitro migration rates of 40 microarray-profiled human bladder cancer cell lines were measured by radial migration assay. Genes whose expression was either directly or inversely associated with cell migration rate were identified and subsequently evaluated for their association with cancer stage in 61 patients. This analysis identified genes known to be associated with cell invasion such as versican, and novel ones, including metallothionein 1E (MT1E) and nicotinamide N-methyltransferase (NNMT), whose expression correlated positively with cancer cell migration and tumor stage. Using loss of function analysis, we show that MT1E and NNMT are necessary for cancer cell migration. These studies provide a general approach to identify the clinically relevant genes in cancer cell migration and mechanistically implicate two novel genes in this process in human bladder cancer.