A study published today in EMBO Molecular Medicine (doi: 10.15252/emmm.201303675) reveals that the loss of function of the gene RARRES3 in breast cancer cells promotes metastasis to the lung. The research, headed by Roger Gomis, ICREA Professor at the Institute for Research in Biomedicine (IRB Barcelona) –based int the parc Científic de Barcelona– is the result of a collaboration between two IRB labs and Joan Massagué, at the Memorial Sloan Kettering Cancer Center in New York.

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The scientists demonstrate that RARRES3 is suppressed in estrogen receptor-negative (ER-) breast cancer tumours, thus stimulating the later invasion of the cancer cells and conferring them “a greater malignant capacity,” says Gomis, head of the Growth control and cancer metastasis lab at the IRB.

This type of tumour accounts for between 20% and 30% of breast cancer cases, the metastasis of which usually occurs in the lung or other soft tissues. This stage of the disease is generally fatal. The studies have been performed in samples from mice and in cell lines and have been validated in 580 samples from primary breast cancer tumours.

The study describes that RARRES3 loss of function allows the breast tumour cell to develop the adhesion capacity of malignant cells when settling in lung tissue. Furthermore, after losing RARRES3 cells also lose differentiation capacity (specialization in a specific cell type), which facilitates the initiation of metastases in distant tissues.

“The transformation of a normal cell into an invasive tumour cell is not just about acquiring capacities but equally important is the loss of certain genes, such as RARRES3,” explains Roger Gomis.

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