Protein That Triggers Cancer Spread Discovered
Researchers in the US have discovered that a protein known as disabled 2 (Dab2) triggers cancer spread by switching on the process that allows cancer cells to migrate from the original tumor site and establish new tumors in other parts of the body.
The researchers have written about their study, which was funded by the National Cancer Institute, in the 14 February advance online issue of Nature Cell Biology.
The project started when co-author Dr. 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, both in Cleveland, Ohio, began investigating what kicks off a process called EMT, epithelial- mesenchymal transdifferientiation, which is already known to play a role in releasing cells from the surface of a tumor and giving them the ability to start a new tumor by changing them from epithelial cells into transient mesenchymal cells.
This step, known as metastasis, when cells begin to leave the original tumor and migrate to other parts of the body and set up new tumors, is often the fatal process in colo-rectal, breast, prostate, ovarian and pancreatic cancers.
Jin decided to work backwards to find out what triggers EMT. Most tumors start in epithelial tissue, a major type of tissue that lines cavities or covers the surface of major structures in the body (other tissue types are connective tissue, muscle tissue and nervous tissue.) Such tumors have epithelial markers on their surface and EMT is when those marker cells dislodge and transform into fibrous mesenchymal cells that can migrate.
Jin, who was part of a six-member team led by co-author Philip Howe from the Department of Cancer Biology at the Lerner Research Institute, told the media that:
“EMT is the most important step in this process.”
Studying the biology of cancer spread in laboratory animals, Jin and colleagues discovered that a protein called transforming growth factor-beta (TGF-beta) triggered the formation of Dab2 and Dab2 activated EMT.
Previous research had already shown that TGF-beta, which principally functions as a tumor suppressor, can also aid tumor growth and metastasis during the late stages of malignant progression.
When they knocked out Dab2, the researchers found that EMT did not kick off.
“This is the major piece in cancer research that has been missing,” said Jin.
The authors concluded that their discovery suggests:
“… the existence of a TGF-beta-inducible post-transcriptional regulon that controls EMT during the development and metastatic progression of tumors.”
Jin described the process as a “complicated cascade”, and explained that:
“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.”
He said the discovery may also help us understand the progression of other diseases.