Cancer’s ability to grow unchecked is often attributed to cancer stem cells, a small fraction of cancer cells that have the capacity to grow and multiply indefinitely. How cancer stem cells retain this property while the bulk of a tumour’s cells do not remains largely unknown. Now, using human tumour samples and mouse models,researchers at University of California, San Diego and Moores Cancer Center have shown that cancer stem cell properties are determined by epigenetic changes, chemical modifications cells use to control which genes are turned on or off. The study is published in the Proceedings of the National Academy of Sciences.
The current showed that an enzyme known as Lysine-Specific Demethylase 1 (LSD1) turns off genes required to maintain cancer stem cell properties in glioblastoma, a highly aggressive form of brain cancer. This epigenetic activity helps explain how glioblastoma can resist treatment. What’s more, state the team, drugs that modify LSD1 levels could provide a new approach to treating glioblastoma.
The researchers first noticed that genetically identical glioblastoma cells isolated from patients differed in their tumourigenicity, or capacity to form tumours, when transplanted to mouse models. This observation suggested that epigenetics, rather than genetics (DNA sequence), determines tumourigenicity in glioblastoma cancer stem cells. They go on to add that one of the most striking findings in the current study is that there are dynamic and reversible transitions between tumourigenic and non-tumourigenic states in glioblastoma that are determined by epigenetic regulation.
Probing further the team discovered that the epigenetic factor determining whether or not glioblastoma cells can proliferate indefinitely as cancer stem cells is their relative abundance of LSD1. LSD1 removes chemical tags known as methyl groups from DNA, turning off a number of genes required for maintaining cancer stem cell properties, including MYC, SOX2, OLIG2 and POU3F2.
The data findings show that this plasticity represents a mechanism by which glioblastoma develops resistance to therapy. For instance, the results show that glioblastomas can escape the killing effects of a drug targeting MYC by simply shutting it off epigenetically and turning it on after the drug is no longer present. The team state that ultimately strategies addressing this dynamic interplay will be needed for effective glioblastoma therapy.
The team stress that the epigenetic changes driving glioblastoma are similar to those that take place during normal human development. The lab surmise that although most cells in the human body contains identical DNA sequences, epigenetic changes help make a liver cell different from a brain cell. They go on to conclude that the results indicate that the same programming processes determine whether a cancer cell can grow indefinitely or not.
brain cancer, cancer, cancer proliferation, cancer stem cell, epigenetic methylation, epigenetics, genetics, glioblastoma, healthinnovations, LSD1, neurogenetics, neuroinnovations, oncogene, stem cell
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.