Translational control of cancer – Ola Larsson's Group

Following transcription, mRNA molecules are translated into proteins. This process is highly regulated to enable selective synthesis of subsets of proteins. The translation of mRNA is dysregulated in multiple diseases including cancer. In cancer, alterations in mRNA translation reshapes the proteome and thereby leads to acquisition of pro-cancer phenotypes. My group aims to understand how translation is dysregulated in cancer, and how mRNA translation can be targeted for anti-cancer treatment.

Our research

Gene expression is regulated post-transcriptionally at multiple levels including mRNA-splicing, -transport, -stability and -translation. Regulation of translation enables quick alterations in gene expression in response to internal and external signals; and highly controlled expression of genes with potentially detrimental functions (e.g. oncogenes). In many cases, mRNA translation is regulated at the level of initiation and therefore involves a shift in the number of ribosomes synthesizing proteins from each mRNA. In addition, we and other research groups have shown that key oncogenic pathways modulate translation by tuning translation elongation. This has expanded the repertoire of mechanisms controlling mRNA translation in health and disease.

Translational can be a regulated globally, by targeting translation of mRNA transcribed from most genes in a similar fashion, or selectively, by targeting subsets of mRNAs. The specificity for regulation depends on features in the mRNA molecule, often found in the untranslated region (UTR) but also in the coding region when regulation occurs at the level of elongation. Regulation of translation depends on interactions between these RNA-features and e.g. translation factors and RNA-binding proteins. A broader understanding of how mRNA translation is regulated and dysregulated in diseases is lacking.

The goal of our research program is to generate knowledge about the organization, specificity and mechanisms acting to control translation at a transcriptome-wide level, and how these mechanisms are affected in e.g. breast cancer. In particular, we aim to understand whether translation defines molecular subtypes of cancer and identify mechanisms that are potential targets for their treatment. This may guide us towards new therapeutic targets for treatment of poor prognosis breast cancers.

Developed software

anota (https://www.bioconductor.org/packages/release/bioc/html/anota.html)

anota2seq (https://bioconductor.org/packages/release/bioc/html/anota2seq.html)

NOMAD (https://github.com/carlmurie/NOMAD)

Funding

  • Swedish Cancer Society
  • Swedish Research Council
  • Knut and Alice Wallenberg Foundation
  • Cancer Research Funds of Radiumhemmet
  • Swedish Brain Foundation

Publications

Selected publications

Members and contact

Group leader

All members of the group