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

Abstract

The cell's repertoire of transfer RNAs (tRNAs) has been linked t cancer. Recently, the level of the initiator methionine tRNA (tRNA Met in stromal fibroblasts has been shown to influence extracellular matri (ECM) secretion to drive tumour growth and angiogenesis. Here w show that increased tRNA Met within cancer cells does not influenc tumour growth, but drives cell migration and invasion via mechanism that is independent from ECM synthesis an dependent on α5β1 integrin and levels of the translation initiatio ternary complex. In vivo and ex vivo migration (but not proliferation) o melanoblasts is significantly enhanced in transgenic mice whic express additional copies of the tRNA Met gene. We show tha increased tRNA Met in melanoma drives migratory, invasive behaviou and metastatic potential without affecting cell proliferation an primary tumour growth, and that expression of RNA polymerase IIIassociate genes (which drive tRNA expression) are elevated i metastases by comparison with primary tumours. Thus, specifi alterations to the cancer cell tRNA repertoire drive a migration invasion programme that may lead to metastasis.