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Researchers Find Gene Responsible for Breast Cancer Metastasis
A particular human gene variant makes breast cancer cells more aggressive, according to a team of international researchers led by scientists at the Medical University of Vienna in Austria. Not only are these cells more resistant to chemotherapy, but they also metastasize to other parts of the body.
The researchers have identified a gene, AF1q, as being substantially responsible for this metastatic activity and have recognized it as a possible starting point for more-accurate diagnosis of breast cancer and for potential targeted therapeutic approaches. Their findings were published in the June 7 issue of Oncotarget.
The human AF1q gene was originally discovered in a chromosomal abnormality and recognized as an important factor in the development of leukemia, according to the authors. Elevated AF1q levels were also found in particularly aggressive forms of acute myeloid leukemia.
The exact function of the AF1q protein in the body is not yet fully understood, the researchers say, but a new study has shown that it has a key role in the TCF7/Wnt signaling pathway and controls the behavior of cancer cells. Increased AF1q expression promotes the development and growth of tumor cells and prevents natural cellular death. Patients with breast cancer who have pronounced AF1q expression have a much poorer prognosis than do those who have not, the investigators say. Furthermore, AF1q-positive cancer cells are more resistant to certain forms of chemotherapy.
The researchers further demonstrated that increased expression of AF1q in breast cancer cells encourages metastasis in the liver and the lungs. When the team compared samples of primary tumors with samples of metastatic tumors, they found that AF1q-positive cancer cells had left the primary tumor and had metastasized to other areas of the body.
“There is a lot of evidence to suggest that cancer cells with hyperactive AF1q expression act like founding cells for metastases,” lead investigator Dr. Lukas Kenner explained. “They are able to migrate into other parts of the body, establish themselves there, and spread.”
Since the increased presence of AF1q indicates a poorer prognosis, this knowledge can be used to improve diagnosis in the future, the authors say. However, AF1q can also be used as a starting point for targeted treatment. For example, it might be possible to reduce the formation of metastases or even prevent it altogether in the future.
Sources: Medical University of Vienna; June 15, 2015; and Oncotarget; June 7, 2015.