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

• Published in: Oncogene Vol. 27; no. 52; pp. 6679 - 6689
• Main Authors: WU, Y, SIADATY, M. S, BERENS, M. E, HAMPTON, G. M, THEODORESCU, D
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 06.11.2008
• Subjects: Biological and medical sciences; Bladder cancer; Cancer; Cell adhesion & migration; Cell migration; Cell Movement; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA microarrays; Extracellular Matrix - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetics; Humans; Medical sciences; Metallothionein; Metallothionein - genetics; Metallothionein - metabolism; Metastases; Metastasis; Methyltransferase; Molecular and cellular biology; Molecular genetics; N-Methyltransferase; Neoplasm Invasiveness; Neoplasm Staging; Nephrology. Urinary tract diseases; Nicotinamide N-methyltransferase; Nicotinamide N-Methyltransferase - genetics; Nicotinamide N-Methyltransferase - metabolism; Oncology; RNA, Small Interfering - genetics; Substrate Specificity; Transcription; Transcription. Transcription factor. Splicing. Rna processing; Tumor cell lines; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary tract diseases; Urinary tract. Prostate gland; Versican; Wound Healing; Human; transcriptional profiling; Urinary system disease; Transcription; Enzyme; Transferases; Migration; Identification; Urinary tract disease; Malignant tumor; Metastasis; Gene expression; Bladder cancer; Carcinogenesis; Mechanism; Gene expression profile; Methyltransferases; mechanism of cell movement; Bladder disease; Metallothionein; Cancer; Nicotinamide N-methyltransferase
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2008.264

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.