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Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration

Oncogene volume 27, pages 6679–6689 (2008)Cite this article

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.

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Acknowledgements

We thank Dr Jay Fox and Dr Yongde Bao of the University of Virginia Array Core facility for their assistance with chip hybridization. We also thank Dr Martin A Schwartz and Dr Konstadinos Moissoglu of the Cardiovascular Research Center, University of Virginia for their assistance with time-lapse microscopy. Mr Christian Beaudry at TGen performed the high-throughput cell migration experiments. This work was supported by NIH grant CA075115 to DT.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA, USA

    Y Wu & D Theodorescu

  2. Department of Public Health Sciences, University of Virginia Health Sciences Center, Charlottesville, VA, USA

    M S Siadaty

  3. Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA

    M E Berens

  4. Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA

    G M Hampton

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Correspondence to D Theodorescu.

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The authors declare that they have no competing financial interests.

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Wu, Y., Siadaty, M., Berens, M. et al. Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration. Oncogene 27, 6679–6689 (2008). https://doi.org/10.1038/onc.2008.264

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