Roger Gomis, Luciano di Croce & Mariona Graupera García Milà

Institut de Recerca Biomèdica, Centre de Regulació Genòmica & Institut de Recerca contra la Leucèmia Josep Carreras

Breast cancer is the most common form of cancer among women, with over 2 million new cases diagnosed each year. In cases where the tumor remains localized in the breast, survival rates are notably high, around 90%. However, the spread of cancer cells beyond the breast tissue and the formation of metastases in other organs drastically worsen the prognosis and pose significant challenges.

Our previous research had already linked the MAF (Musculoaponeurotic fibrosarcoma oncogene homolog) protein to an increased risk of developing metastasis and resistance to a treatment known as “adjuvant bisphosphonates” used to prevent breast cancer metastasis to the bone, but the reasons for this connection remained unclear.

This study has revealed the mechanism by which the MAF protein increases the risk of metastasis in breast cancer patients. This discovery provides pivotal understanding of the molecular basis of metastasis and has relevant clinical implications for treatment. In this Nature Cell Biology issue, we report how the MAF protein interacts with the estrogen receptor, central in breast cancer development. This interaction causes genome DNA chromatin remodeling, and targets the activation of genes favoring metastasis, particularly in response to estrogen. Cancers expressing high levels of MAF protein have a greater risk of developing metastasis.

This study opens the possibility of preventing metastasis by inhibiting the activation of pro-metastatic genes through the inhibition of KDM1A, which is responsible for the chromatin remodeling. This opens new perspectives in the treatment of breast cancer. The detection of high levels of MAF predicts the risk of metastasis, as well as an inadequate response to adjuvant bisphosphonates. This information is particularly crucial for young and premenopausal patients.

Treatments targeting the bone metastasis environment can, in some cases, redirect metastasis to other organs, negatively impacting overall patient survival.