Metastatic breast cancer is breast cancer that has spread to another part of the body, most commonly the bones, lungs, brain, or liver. Researchers from the University of Geneva (UNIGE), in collaboration with researchers from ETH Zurich (ETHZ), sought to determine the reason why cancer cells in breast cancer may spread to the bones. The researchers identified a protein in mice that may be behind the phenomenon. This discovery could lead to the development of therapeutic approaches to suppress metastasis.

These findings were published in the journal Nature Communications, in a paper titled, “Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis.”

“The epithelial to mesenchymal transition (EMT) has been proposed to contribute to the metastatic spread of breast cancer cells,” the researchers wrote. “EMT-promoting transcription factors determine a continuum of different EMT states. In contrast, estrogen receptor α (ERα) helps to maintain the epithelial phenotype of breast cancer cells and its expression is crucial for effective endocrine therapies. Determining whether and how EMT-associated transcription factors such as ZEB1 modulate ERα signaling during early stages of EMT could promote the discovery of therapeutic approaches to suppress metastasis.”

In the case of metastatic breast cancer, the cancer cells primarily colonize the bones, but can also be found in other organs such as the liver, lungs, or brain.

Although the molecular and cellular mechanisms responsible for the different stages of the metastatic process are not yet fully understood, studies show that cellular plasticity plays an important role.

The laboratory of Didier Picard, PhD, professor, department of molecular and cellular biology at the Faculty of Science, UNIGE, is interested in the mechanisms that govern the metastatic processes related to breast cancer. His group collaborated with Nicolas Aceto’s group at ETHZ to study these processes in mice. The biologists investigated the potential role of the protein ZEB1, known to increase cell plasticity, in breast cancer cell migration.

‘‘Unlike in women, mice transplanted with human breast cancer cells develop metastasis to the lungs, not the bones,’’ said Nastaran Mohammadi Ghahhari, researcher in the department of molecular and cell biology and first author of the study. ‘‘We therefore sought to identify factors capable of inducing metastasis in bone tissue and in particular tested the effect of the factor ZEB1.’’

The researchers discovered that cancer cells expressing ZEB1 moved to bone tissue, unlike cancer cells that did not express it. These results were later confirmed when human breast cancer cells were transplanted into the mammary glands of mice.

‘‘We can therefore assume that this factor is expressed during tumor formation and that it directs cells that have acquired metastatic characteristics to the bones,’’ concluded Picard, the study’s last author. This study confirms the importance of the plasticity of tumor cells during the metastatic process and could allow, in the long term, to consider new therapeutic approaches to prevent the appearance of metastases.