Findings offer clue to how molecule can both stimulate, suppress cell growth
Study provides insight into role of TGF-beta in cancer development, progression
Scientists are puzzled by the fact that the molecule known as transforming growth factor-beta (TGF-b) generally stops cells from multiplying but at other times promotes cell growth.
Dr. Hal Moses, director of the Vanderbilt-Ingram Cancer Center, and his lab identified TGF-b in 1985 as both a growth stimulator and growth suppressor. Since that time, its role in colon, breast and other cancers has been studied extensively at Vanderbilt and elsewhere.
Now a team of researchers at Vanderbilt-Ingram has found a clue to the seemingly contradictory biological actions of TGF-b. Their findings are published online this week by the Proceedings of the National Academy of Science (www.pnas.org) and is expected to appear in the print version later this month.
“TGF-b usually causes cell growth inhibition; however, many solid tumors over-express TGF-b and the cells arent inhibited at all – in fact, sometimes they grow faster than normal as a result of TGF-b signaling,” said Neil A. Bhowmick, Ph.D., assistant professor of Urologic Surgery and senior author on the paper. “Many researchers have studied the ways in which TGF-b suppresses cell growth but not many have examined how it promotes cell growth.”
The researchers studied normal cells lines whose growth was inhibited by TGF-b — the process was working properly – as well as cell lines whose growth was stimulated by TGF-b.
TGF-b uses multiple signaling pathways to get its instructions to the cells nucleus – at least four pathways that are known, and there are probably more, Bhowmick said.
In the inhibited cells, the researchers removed particular protein components in one of these known TGF-b signaling pathways called Rho-ROCK. The cells were no longer inhibited and instead began growing again.
Then they did the opposite, adding the protein components to cells whose growth was being stimulated by TGF-b to see if their growth would be arrested again – that is, if normal TGF-b function would be restored by restoring the pathway. “Lo and behold, thats exactly what happened,” Bhowmick said.
The findings suggest that the Rho-ROCK signaling pathway, traditionally known for its involvement in cell differentiation and defining cell shape, plays a key role in TGF-b inhibition of cell growth. “Perhaps inactivation of this pathway is a way that cancer cells override the normal growth-suppressing activity of TGF-b,” Bhowmick said.
More work is needed to fully understand the implications, but the findings also suggest a potential target for therapeutic intervention to restore TGF-bs ability to inhibit cell growth, he said.
Bhowmicks co-authors on the paper were Mayshan Ghiassi, Mary Aakre, Kimberly Brown, Vikas Singh and Moses, members of the department of Cancer Biology and the Frances Williams Preston Laboratories, supported by the T.J. Martell Foundation at Vanderbilt-Ingram.
The work was supported by the U.S. Department of Defense, the National Cancer Institute and the Vanderbilt-Ingram Cancer Center.
The Vanderbilt-Ingram Cancer Center is the only National Cancer Institute-designated Comprehensive Cancer Center in Tennessee and one of only 38 in the United States. This designation is the highest awarded by the NCI, one of the National Institutes of Health and worlds foremost authority on cancer. It recognizes excellence in all aspects of cancer research, the development of innovative new therapies and a demonstrated commitment to the community through education, information and outreach. For more information, visit www.vicc.org.
All news from this category: Life Sciences and Chemistry
Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.
Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.
German National HPC Centre provides resources to look for cracks in the standard model
Physicists have spent 20 years trying to more precisely measure the so-called “magnetic moment” of subatomic particles called muons. Findings published this week call into question long-standing assumptions of particle…
Designing better antibody drugs with artificial intelligence
Antibodies are not only produced by our immune cells to fight viruses and other pathogens in the body. For a few decades now, medicine has also been using antibodies produced…
New NASA visualization probes the light-bending dance of binary black holes
A pair of orbiting black holes millions of times the Sun’s mass perform a hypnotic pas de deux in a new NASA visualization. The movie traces how the black holes…