Researchers have discovered new properties of the protein involved in metastasis

Another important piece in the mosaic of knowledge about the development and prognosis of breast cancer has been added by a team of scientists from the Masaryk Memorial Cancer Institute and the Faculty of Science of Masaryk University (MU), along with their long-term partners in France and Switzerland. The prestigious journal Molecular and Cellular Proteomics, which ranks among the ten most cited in the field, published the results of research in which researchers discovered and described how a protein works, what its functions are and how it interacts with other proteins. The work will be of key importance, especially in the development of new therapeutic approaches.

18 Feb 2022 Tereza Fojtová

A team of scientists led by Pavel Bouchal from the MU Faculty of Science and Roman Hrstka from the Masaryk Memorial Cancer Institute. Photo: Martin Indruch

It has long been known that, when AGR2 protein levels increase, the prognosis of breast cancer is poor. Tumours are more aggressive, more resistant to treatment and have a greater tendency to metastasise; however, it was not known what role the protein played, why, and which other proteins it interacts with”, said Roman Hrstka from the Masaryk Memorial Cancer Institute. To answer this, the oncologists teamed up with biochemists from the Faculty of Science MU, who were the only researchers in the Czech Republic at that time to have technologies that allowed them to describe how this protein works in the cell, what other proteins it binds to and what it affects.

We used a number of advanced analytical techniques, including liquid chromatography in combination with mass spectrometry, to identify the protein and its interaction partners, i.e. the other proteins it acts on, and describe how it interacts”, explained Pavel Bouchal from the Department of Biochemistry, Faculty of Science MU. The AGR2 protein belongs to a family of enzymes whose task is to ensure that other proteins are properly assembled so that they can perform their individual functions. On the one hand, the AGR2 protein appears to ensure the proper assembly of other proteins inside the cell, but contributes to the metastasis of tumour cells when it comes out of the cell.

Roman Hrstka. Photo: Martin Indruch
Pavel Bouchal. Photo: Martin Indruch

The very existence of the AGR2 protein is important for the organism. In terms of evolution, we find it in amphibians to mammals, where it has a physiological role, playing an important role in embryo development and regeneration processes, for example. In the case of adults that undergo malignant transformation, this physiological role is suppressed and the protein may, in turn, contribute to the development of cancer. “If we can accurately distinguish interactions with proteins that are desirable from those where it is better to avoid interactions, we will be able to use it in the treatment of cancer”, said Hrstka.

Localisation of AGR2 and PDIA3 proteins in A549 lung cancer tumour cells, using fluorescence microscopy.

In order for the researchers to know what to focus on, it was first necessary to describe which proteins the AGR2 protein binds to, which it can influence in some way due to its properties and how it does so. “We found that the tumour cell exports some of these proteins, including AGR2, from the inside out. The proteins then start working somewhere outside the tumour cell and thus contribute to the formation of another tumour site, i.e. metastasis”, said Bouchal, while outlining the direction that further research will take.

A total of 12 scientists worked on the results, with colleagues from the universities of Rennes and Geneva collaborating on the published results. Loschmidt’s protein engineering laboratories at the Faculty of Science MU played a significant role in the theoretical modelling of protein interactions. The research was funded by the Grant Agency of the Czech Republic and the Ministry of Health of the Czech Republic, and through project funding from European operational programs and the National Sustainability Program.

A team of scientists led by Pavel Bouchal from the MU Faculty of Science and Roman Hrstka from the Masaryk Memorial Cancer Institute. Photo: Martin Indruch

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