A research group led by Professor Lea Sistonen at Åbo Akademi University, Finland, has discovered a new mechanism that regulates breast cancer progression.

Breast cancer arises when the epithelial cells lining the breast ducts become malignant and begin to divide uncontrollably. As the cancer advances, the cells acquire the ability to move, enabling them to spread into the surrounding breast tissue and eventually to other parts of the body. Cancer progression is dependent on phenotypic changes of the tumor cells, but the mechanisms controlling these changes at the molecular level are still poorly understood.

– The Sistonen group has previously reported that the amount of the human stress protein HSF2 varies when cells undergo phenotypic changes during normal cell growth and development. However, it has remained unknown how HSF2 levels are regulated in different pathological conditions, such as cancer. The purpose of this study was to investigate how HSF2 affects breast cancer progression, says doctoral researcher Jenny Pessa from Cell and Molecular Biosciences program at Åbo Akademi University.

The work utilized patient tissue samples as well as cell-derived cancer models in mice and zebrafish. The results revealed that in the early stage of breast cancer, high levels of HSF2 promote cell division and tumor growth. In contrast, in later stages, reduced HSF2 is required to induce cell motility and invasion into surrounding tissues. Using molecular biology methods, the group also identified the specific signaling pathway that regulates the decrease in HSF2 levels upon invasive transition.

– We discovered a molecular switch, which allows cancer cells to transition from a proliferative to an invasive state and initiate aggressive spreading, says Professor Lea Sistonen.

In addition to the altered amount of HSF2 protein, another significant finding was that its localization within tumors changes as the cancer progresses. In early-stage breast cancer, HSF2 is found in the areas of active cell proliferation and tumor growth, a pattern that can no longer be observed at later stages. In clinical breast cancer diagnostics, large tumor areas are often examined to classify the tumor as accurately as possible. According to the results obtained, the levels and localization pattern of HSF2 could give indications of disease progression, proposing HSF2 as a new biomarker to improve prognosis and treatment efficacy of breast cancer patients.

– We still need a lot of basic research at the molecular level as well as thorough analyses of larger patient cohorts. Nevertheless, our findings indicate that understanding the different stages of cancer progression and examining the dynamic changes within tumor regions are important next steps in breast cancer research, Sistonen clarifies.

The study was carried out in collaboration with Associate Professor Emilia Peuhu’s research group at the University of Turku. The research was funded by the Research Council of Finland, Cancer Foundation Finland, the Finnish Cultural Foundation, the Sigrid Jusélius Foundation, and the Jane and Aatos Erkko Foundation.

The research article has been published in the prestigious scientific journal Science Advances 3.9.2025.