Translation reprogramming through wobble tRNA modification in cancer.

cancer • protein reprogramming • transfer RNA

Pierre Close is Research Associate at the FNRS and manages the Cancer Signalling Laboratory in the GIGA research centre
(Université de Liège). The regulation of mRNA translation has emerged as a central mechanism driving the adaptation of tumour cells during cancer progression and response to treatment. Cancer cells thus adapt to a hostile environment using a protein reprogramming mechanism (the modification of the mRNA translation “programme” into proteins).

This project is dedicated to the modification of transfer RNA (tRNA) on their “wobble” base ( the 5’ base of the anti-codon).  The project is based on the hypothesis that this modification represents a new mechanism, which allows protein translation to be reprogrammed in cancers and supports the expression of specific proteomes that are required for the survival of cancer cells, the formation of metastases and resistance to treatment. During the first two years, Pierre Close and his team have discovered the central role of tRNA base modification in the resistance of melanoma to targeted therapies, through the establishment of specific oncogenic proteomes. It has been demonstrated that targeting this process is an important therapeutic option in patients with resistant melanoma. The next stage of the project will study codon-specific translation during cancer development and in the tumour micro-environment.

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