The mystery behind how a protein, TGF-beta, can prevent cancer from forming and encourage its aggressive growth in human cell, has been discovered by a team of researchers.
The findings could provide a potential target for treatment with the new insight into the cancer mystery that is considered to be a major paradox of cancer biology. TGF-beta is known as a tumor suppressor, which is necessary to keep cells in check and growing normally.
However, at some point, its function flips and it becomes a tumor promoter, fostering aggressive growth and spread of cancer. The researchers identified Bub1 as a key gene involved in regulating TGF-beta receptor.
“Bub1 is well-known for its role in cell division. But this is the first study that links it to TGF-beta. We think this may explain the paradox of TGF-beta as a tumour promoter and a tumour suppressor,” said study director Alnawaz Rehemtulla from University of Michigan Medical School.
“Our data that Bub1 is involved at the receptor level is completely unexpected,” Rehemtulla added. The team of researchers developed a way to screen for genes that regulate the TGF-beta receptor.
TGF-beta is known to play a role in cells developing characteristics of aggressive cancer cells. Researchers also have known that Bub1 is highly expressed in many different types of cancer. When 720 genes from the human genome were screened against lung cancer and breast cancer cells, Bub1 emerged as playing a strong role in TGF-beta signaling.
Bub1 was shown to bind to the TGF-beta receptor and allows it to turn on aggressive cell growth. When the researchers blocked Bub1, it shut down the TGF-beta pathway completely because Bub1 is found in many types of cancer, developing a drug to target it could potentially impact multiple cancers.
“When you look at gene expression in cancer, Bub1 is in the top five. In addition, Bub1 expression levels correlate with outcome in patients with lung and breast cancer. But we never knew why. Now that we have that link, we’re a step closer to shutting down this cycle,” said Rehemtulla.
The study was in Science Signaling, a journal published by the American Association for the Advancement of Science.