New mechanism explaining how cancer cells spread highlighted by international collaboration
UT Southwestern Medical Center cancer researchers have identified a protein critical to the spread of deadly cancer cells and determined how it works, paving the way for potential use in diagnosis and eventually possible therapeutic drugs to halt or slow the spread of cancer.
The protein, Aiolos, is produced by normal blood cells but commits a kind of "identity theft" of blood cells when expressed by cancer cells, allowing the latter to metastasize, or spread, to other parts of the body. Metastatic cancer cells have the ability to break free from tissue, circulate in the blood stream, and form tumors all over the body, in a way acting like blood cells.
"This is an important discovery because the metastatic spread of tumors accounts for the vast majority of cancer-related deaths. Now that we know the role of Aiolos, we can look toward therapeutic intervention," said Dr. Lance Terada, Professor of Internal Medicine and Chief of the Division of Pulmonary/Critical Medicine at UT Southwestern.
The research, available online and in the journal Cancer Cell, found that Aiolos, which frequently is expressed in lung cancers, is a predictor of a markedly worse prognosis in lung cancer patients.
Aiolos is a member of a class of proteins called transcription factors - proteins that control which genes are turned on or off by binding to DNA and other proteins. Once bound to DNA, these proteins can promote or block the enzyme that controls the reading, or "transcription," of genes, making genes more or less active.
Aiolos decreases the production of cell adhesion proteins and disrupts critical cell adhesion processes, including processes that allow tissue cells to anchor to their physical environment, a necessary requirement for cells to survive and spread. Metastatic cells don't need this adhesion, allowing them to proliferate instead. Aiolos also represses another protein called p66Shc, which otherwise would suppress metastatic ability, which is the ability of the cancer cells to spread.
"Despite their importance, cellular behaviors that are largely responsible for cancer mortality are poorly understood," Dr. Terada said. "Our study reveals a central mechanism by which cancer cells acquire blood cell characteristics to gain metastatic ability and furthers our understanding in this area."
The research was done in collaboration with a team from the Tianjin Medical University, China, led by Dr. Zhe Liu, a former postdoctoral research fellow of Dr. Terada and co-corresponding author on the paper. Other UT Southwestern researchers involved include Dr. John Minna, Professor of the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research, Internal Medicine, and Pharmacology, and Dr. Luc Girard, Assistant Professor of Pharmacology.
Dr. Minna and Dr. Girard are members of UT Southwestern's Harold C. Simmons Cancer Center, the only National Cancer Institute-designated cancer center in North Texas and one of just 66 NCI-designated cancer centers in the nation. The Harold C. Simmons Comprehensive Cancer Center includes 13 major cancer care programs with a focus on treating the whole patient with innovative treatments, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians.
The work was supported by the Ministry of Science and technology of China, the National Natural Science Foundation of China, the Tianjin Municipal Science and Technology Commission, the specialized Fund for Doctoral Program of Higher Education, the China Postdoctoral Science Foundation, the James M. Collins for Biomedical Research, and the National Institutes of Health.