Dental researcher finds switch that turns on the spread of cancer

Feb 14, 2010

Reporting in Nature Cell Biology, researchers describe the discovery of a specific protein called disabled-2 (Dab2) that switches on the process that releases cancer cells from the original tumor and allows the cells to spread and develop into new tumors in other parts of the body.

The process called epithelial-mesenchymal transdifferientiation (EMT) has been known to play a role in releasing cells (epithelial cells) on the surface of the solid tumor and transforming them into transient mesenchymal cell: cells with the ability to start to grow a new tumor.

This is often the fatal process in breast, ovarian, pancreatic and colon-rectal cancers.

Searching to understand how the EMT process begins, Ge Jin, who has joint appointments at the Case Western Reserve University School of Dental Medicine and the Lerner Research Institute at the Cleveland Clinic, began by working backwards from EMT to find its trigger.

The researchers found that a compound called transforming growth factor-ß (TGF-ß) triggers the formation of the Dab2 protein. It was this protein, Dab2, that activated the EMT process.

He discovered that when the researchers knocked out Dab2, EMT was not triggered.

"This is the major piece in research that has been missing," Jin said.

Most tumors are epithelial in origin and have epithelial markers on their surface. The EMT process takes place when some of those cells dislodge from the surface and undergo a transformation into a fibrous mesenchymal cell maker with the ability to migrate.

"EMT is the most important step in this process," said Jin. He was part of a six-member research team, led by Philip Howe from the Department of Cancer Biology at the Lerner Research Institute in a National Cancer Institute-funded study.

The research group studied the biological processes that initiated the cancer spread by using in animal models.

"It's a complicated cascade process," Jin said.

"If we can understand the signaling pathway for modulating EMT, then we can design drugs to delay or halt EMT cells and control tumor progression," Jin said.

Beyond cancer, Jin said. "The process we discovered may lead to understanding how other diseases progress."

Explore further: Target growth-driving cells within tumors, not fastest-proliferating cells

More information: TGF-ß-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI, Arindam Chaudhury and George S. Hussey, Nature Cell Biology.

Related Stories

Embryonic pathway delivers stem cell traits

May 15, 2008

Studies of how cancer cells spread have led to a surprising discovery about the creation of cells with adult stem cell characteristics, offering potentially major implications for regenerative medicine and ...

Fibroblasts invade at a snail's pace

Feb 02, 2009

A transcription factor known to drive the formation of fibroblasts during development also promotes their ability to invade and remodel surrounding tissues, report Rowe et al. in the February 9, 2009 issue ...

Recommended for you

Same cancer, different time zone

7 hours ago

Just as no two people possess the same genetic makeup, a recent study has shown that no two single tumor cells in breast cancer patients have an identical genome.

Brazilian researchers identify RNA that regulates cell death

11 hours ago

Researchers from the University of São Paulo (USP) have identified an RNA known as INXS that, although containing no instructions for the production of a protein, modulates the action of an important gene in the process ...

User comments : 0