The gene SRC-3 (steroid receptor co-activator 3) is not only involved in breast cancer growth but also in metastases, according to Baylor College of Medicine (BCM) researchers and collaborators. They were able to determine how the gene sends a signal to the cell membrane to promote cell motility. The research appears in the current issue of Molecular Cell.
SRC-3 is reportedly overexpressed in two-thirds of breast cancers. It is also known that SRC-3 enhances estrogen-dependent growth of cancer cells by activating and encouraging the transcription of a genetic message into a protein. However, how the message to invade other cells gets from the epidermal growth factor receptor (EGFR) to the activating enzyme called FAK (focal adhesion kinase) found on the cell's membrane had not been determined, notes Bert O'Malley, M.D., chair of molecular and cellular biology at BCM and the report's senior author.
Dr. O’Malley’s current research uncovered new activity for SRC-3 at the cell's periphery. They found that the gene can produce a shorter form of its co-activator protein that is missing the part that keeps it in the nucleus. With this exon gone, it is free to travel into the cytoplasm and to the membrane, Dr. O’Malley explains. “At the membrane, the enzyme PAK1 phosphorylates SRC-3, allowing it to function at the membrane.”
The finding explains how the epidermal growth factor receptor at the membrane gets a signal to the enzyme that tells the cell to move and ultimately grow, allowing the cancer to invade surrounding tissue, Dr. O'Malley adds.
“Now we have a final picture as to why epidermal growth factor receptor and the estrogen receptor are the most dangerous combination of molecules overproduced in breast cancer. When they are both overfunctioning, people die quickly and are resistant to therapy,” Dr. O’Malley points out.