Researchers uncover key cancer-promoting gene

January 6, 2015, University of Michigan Health System

One of the mysteries in cancer biology is how one protein, TGF-beta, can both stop cancer from forming and encourage its aggressive growth.

Now, researchers at the University of Michigan Comprehensive Cancer Center have uncovered a key gene that may explain this paradox and provide a potential target for treatment.

TGF-beta is known as a tumor suppressor, meaning it's necessary to keep cells in check and growing normally. But at some point, its function flips and it becomes a , fostering aggressive growth and spread of cancer. The researchers identified Bub1 as a key gene involved in regulating TGF-beta receptor.

The study is published in Science Signaling.

"Our data that Bub1 is involved at the receptor level is completely unexpected," says study director Alnawaz Rehemtulla, Ph.D., Ruth Tuttle Freeman Research Professor of radiation oncology and radiology and co-director of the Center for Molecular Imaging at the University of Michigan Medical School.

"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 tumor promoter and a ," he adds.

The team of researchers at the University of Michigan, including Shyam Nyati, Ph.D., and Brian D. Ross, Ph.D., developed a way to screen for genes that regulate the TGF-beta receptor. When 720 genes from the human genome were screened against and , 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.

TGF-beta is known to play a role in cells developing characteristics of aggressive . Researchers also have known that Bub1 is highly expressed in many different types of cancer.

Because Bub1 is found in many types of cancer, developing a drug to target it could potentially impact multiple cancers. A compound to target Bub1 has been developed but is not ready for testing in patients. Initial lab testing suggests that a Bub1 inhibitor can very specifically target Bub1 without causing damage to other parts of the cell.

"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 . But we never knew why. Now that we have that link, we're a step closer to shutting down this cycle," Rehemtulla says.

Explore further: Study details on-off switch that promotes or suppresses breast cancer

More information: Science Signaling, Vol. 8, Issue 358, Jan. 6, 2015.

Related Stories

Study details on-off switch that promotes or suppresses breast cancer

February 16, 2012
Signals can tell cells to act cancerous, surviving, growing and reproducing out of control. And signals can also tell cells with cancerous characteristics to stop growing or to die. In breast cancer, one tricky signal called ...

Discovery of protein that fuels breast cancer growth could lead to targeted treatment

September 12, 2012
(Medical Xpress)—Cancer Research UK scientists have discovered how a key protein fuels breast cancer growth by boosting numbers of cancer stem cells in tumours that have low levels of a protein called claudin, accounting ...

Survival molecule helps cancer cells hide from the immune system

October 7, 2014
A molecule that helps cancer cells evade programmed self-destruction, an internal source of death, might also help malignant cells hide from the immune system, an external source of death.

Retinoblastoma dysfunction promotes pancreatic cancer cell growth

December 16, 2013
Indiana University cancer researchers have discovered that a protein that normally suppresses tumors actually promotes the growth and spread of pancreatic cancer.

Ovarian cancer cells hijack surrounding tissues to enhance tumor growth

September 4, 2012
Tumor growth is dependent on interactions between cancer cells and adjacent normal tissue, or stroma. Stromal cells can stimulate the growth of tumor cells; however it is unclear if tumor cells can influence the stroma.

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Shapoval
not rated yet Jan 12, 2015
Iron-Related Cancer-Promoting Genes Uncovered. Now, researchers at the University of Michigan Comprehensive Cancer Center have uncovered a key gene Bub1 involved in regulating TGF-beta receptor. Primary tumors always develop at body sites of excessive iron deposits. Local/regional iron overload can be inherited or acquired. Iron disorders are inherited and can be confirmed with genetic testing. At the cellular level, cancer occurs when cellular iron overload affects cellular organelles. Cellular iron overload can chaotically affect DNA, chromosomes, mitochondria, lysosomes, etc. The Father of Oncology recognizes that cancers are caused by iron-related genes or/and iron-related events. Chemical carcinogens, radiation, viruses, old age and some lifestyle factors non-genetically distort iron metabolism and create local/regional deposits within different tissues and organs. Clinical iron-deficiency methods will beat iron-related diseases (cancers).

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.