The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma

Birch, J. et al. (2016) The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma. Biology Open, 5(10), pp. 1371-1379. (doi: 10.1242/bio.019075) (PMID:27543055) (PMCID:PMC5087684)

Abstract

The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, levels of the initiator methionine tRNA (tRNAiMet) in stromal fibroblasts have been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAiMet within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex. In vivo and ex vivo migration (but not proliferation) of melanoblasts is significantly enhanced in transgenic mice which express additional copies of the tRNAiMet gene. We show that increased tRNAiMet in melanoma drives migratory, invasive behaviour and metastatic potential without affecting cell proliferation and primary tumour growth, and that expression of RNA polymerase III-associated genes (which drive tRNA expression) are elevated in metastases by comparison with primary tumours. Thus specific alterations to the cancer cell tRNA repertoire drive a migration/invasion programme that may lead to metastasis.

• Item Type: Articles
• Additional Information: This work was funded by Cancer Research UK grant number C596/A18277.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Blyth, Professor Karen and Norman, Professor James and Birch, Dr Joanna and Liko, Dr Dritan and Mitchell, Mrs Louise and Campbell, Dr Kirsteen and Kalna, Dr Gabriela and Clarke, Dr Cassie and Neilson, Dr Matthew and Strathdee, Mr Douglas and Sansom, Professor Owen and Campbell, Dr Andrew
• Authors: Birch, J., Clarke, C., Campbell, A. D., Campbell, K., Mitchell, L., Liko, D., Kalna, G., Strathdee, D., Sansom, O. J., Neilson, M., Blyth, K., and Norman, J. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Biology Open
• Publisher: Company of Biologists
• ISSN: 2046-6390
• Published Online: 19 August 2016
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Biology Open 5(10):1371-1379
• Publisher Policy: Reproduced under a Creative Commons License