RNA and cancer: the translation process influenced by multiple factors
Over the past few months, it has been garnering attention in the news. The development of therapeutic mRNAs has benefited from more than 20 years of research on mRNA. For instance, Stéphan Vagner’s team at Institut Curie, in collaboration with Caroline Robert, a clinician at Gustave Roussy, has examined the mechanisms regulating the “translation” of mRNA into proteins in cancer for many years.
Tumor progression, plasticity of cancerous cells, therapy resistance... their analysis reveals complex processes that differ depending on the types of cancer and the treatments received. Published in the September 2021 issue of Nature Reviews Cancer, their analysis paves the way for the development of new antitumor therapeutic targets or treatment combinations.
In the cells, gene expression is governed by at least 2 key steps: transcription of genes into messenger RNAs (mRNAs) and then mRNA translation, the process by which proteins are synthesized from mRNAs. At Institut Curie, Lucilla Fabbri and Alina Chakraborty, post-doctoral researchers in the “Biology of RNA, signaling and cancer” unit (Institut Curie, CNRS, Inserm) headed by Stéphan Vagner, are working on the regulation and plasticity of mRNA translation in cancer biology. Along with their colleague from Gustave Roussy, they have just published a review article in Nature Reviews Cancer.
Translation regulation is a determining factor in cell responses
The researchers report that the mRNA translation process is highly dynamic and enables the cell to achieve rapid changes in the synthesis rate of proteins and thus to effectively respond to intra- and extracellular signals. A number of actors are involved in this regulation, including hundreds of regulatory translation factors, RNA binding proteins, ribosomal proteins, as well as hundreds or even thousands of non-coding RNAs.
Decoding mRNA translation to develop new therapies
During tumor progression, activation of intracellular pathways and microenvironmental stresses occur, leading to deregulation of mRNA translation, which itself influences tumor cells. Analyzing and understanding this plasticity is vital to understanding the phenomena of tumor progression and therapy resistance. What are the factors involved in these processes, depending on the types of cancer and treatments received? This is what the researchers analyzed. They also discovered how this regulation occurs in response to targeted therapies and to cancer immunotherapies.
Regulation of mRNA translation is a key determinant of cancer progression and therapy resistance. Translational control is therefore a vulnerability of cancer that can be targeted to limit its progression and overcome therapy resistance
explains Stéphan Vagner.
« We are currently considering new therapeutic approaches that could specifically target the translation of cancer-related subset of mRNAs ».
Fabbri, L., Chakraborty, A., Robert, C., Vagner S. The plasticity of mRNA translation during cancer progression and therapy resistance. Nat Rev Cancer 21, 558–577 (2021). https://doi.org/10.1038/s41568-021-00380-y