Cancer researchers at the University of Texas Southwestern Medical Center recently identified Aiolos as a critical protein involved in the spread of deadly cancer cells and also revealed how the protein works. Ultimately, further research could lead the way for the development of possible therapeutic drugs to halt or slow the spread of cancer.
The team, led by Dr. Lance Terada, professor of internal medicine and chief of Division of Pulmonary/Critical Medicine at UT Southwestern, made the discovery after studying the anchorage of tissue cells to their physical environment, a requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. In the study, published in the journal Cancer Cell, they found that Aiolos, a lymphocyte lineage-restricted transcription factor, is frequently present in lung cancers and can be related to significantly reduced patient survival.
As the team discovered in its research, Aiolos disrupts cell-cell and cell-matrix interactions by decreasing the amount of a large set of adhesion-related genes. In addition, it reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66Shc and blocking anoikis both in vitro and in vivo.
Finally, researchers found that the p66Shc expression in Aiolos inversely correlates with that of lung cancer tissues and single cells. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic tumors, an important discovery considering that the metastatic spread of tumors accounts for the vast majority of cancer-related deaths, Dr. Terada says. “Now that we know the role of Aiolos, we can look toward therapeutic intervention,” he added.
Furthermore, the study reveals a central mechanism by which cancer cells acquire blood cell characteristics to gain metastatic ability, widening researchers’ knowledge in this area.
The research was conducted in collaboration with a team of scientists from the Tianjin Medical University in China, led by Dr. Zhe Liu, a former postdoctoral research fellow of Dr. Terada’s, and co-corresponding author on the paper. Other UT Southwestern researchers 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.
The research 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.