Researchers target protein involved in cancer stem cell replication
University of Michigan researchers have illuminated steps of the molecular mechanism that increases the overall output of cells during normal brain development. The findings may provide a new strategy for halting the unchecked expansion of cancer stem cells in the brain.
Investigators in the lab of Cheng-Yu Lee at the Life Sciences Institute identified a mechanism that allows neural stem cells to produce “intermediate progenitor cells” in every cell division. These intermediate progenitor cells undergo limited rounds of cell divisions to generate multiple types of cells in the brain.
The ability of neural stem cells to generate intermediate progenitor cells is important for brain development; loss of this ability causes a shortage of cells, while defective intermediate progenitor cells results in the formation of tumors. The findings were published in the journal eLife on October 6.
Researchers in the Lee lab used fruit fly brain cells cultured in the laboratory to show that an evolutionarily conserved enzyme called Trithorax has an important role in maintaining the ability of neural stem cells to repeatedly generate intermediate progenitor cells by keeping regions of chromatin — a macromolecule made of DNA and proteins called histones — in an active state. These active regions contain key genes that can be manipulated to control Trithorax activity and in turn control the production of intermediate progenitor cells.
“Trithorax in Drosophila is closely related to similar enzymes in humans, and our findings suggest that the Trithorax pathway is a potential target for certain brain tumors,” said Hideyuki Komori, a research investigator in the Lee lab and first author on the paper.
Next, the researchers plan to investigate more into this stem cell pathway to seek a strategy for controlling cell growth and division seen in metastatic brain cancers.
“If we can eliminate the ability of cancer stem cells to generate intermediate progenitor cells by reducing the activity of Trithorax, we might be able to slow down or even halt the expansion of tumor mass,” Lee said. “We might be able to design therapies to trick cancer stem cells into generating non-cancerous cell types instead.”
Cheng-Yu Lee is a research professor at the U-M Life Sciences Institute, where his laboratory is located and his research is conducted. He is an assistant professor in the Division of Molecular Medicine and Genetics at the U-M Medical School’s Department of Internal Medicine, and a faculty mentor in the Cellular and Molecular Biology graduate program.
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Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead, eLife. DOI: 10.7554/eLife.03502