Cancer is infamous for its evasive and unrestrained proliferation, which is attributed to a smaller fraction of cancer cells called cancer stem cells. Researchers at the University of California, San Diego School of Medicine and Moores Cancer Center studied glioblastoma, a highly aggressive form of brain cancer, and noticed that genetically identical human glioblastoma cells differed in their tumorigenicity when transplanted into mice. From this, they discovered that cancer stem cell properties are defined by epigenetic changes, which are chemical modifications to the genome that cells use to control and regulate gene activity, rather than genetic changes. In this study, researchers reported that an enzyme known as Lysine-Specific Demethylase 1 (LSD1) switches off genes that are required to maintain cancer stem cell properties in glioblastoma, and that the abundance of LSD1 in the cells is the epigenetic factor that determines whether or not glioblastoma cells can propagate indefinitely as cancer stem cells.
How does LSD1 do this exactly? Simply put, LSD1 removes methyl groups from DNA, or demethylases DNA, which turns off a number genes required for maintaining cancer stem cell properties, such as MYC, SOX2, OLIG2 and POU3F2. With these findings, Clark Chen, one of the study’s first authors, commented on how this mechanism could elucidate resistance to cancer therapy: for example, in the presence of a drug targeting MYC, glioblastomas can escape the lethal effects by shutting it off epigenetically, and turning it on once the drug is no longer present. In conclusion, this discovery leads to the possibility of creating drugs that modify LSD1 levels.
Summary courtesy of Sean Ihn
References:
Epigenetic Driver of Glioblastoma Provides New Therapeutic Target
