Researchers at the University of Kentucky Markey Cancer Center have identified an avenue in pre-clinical models to treat non-small cell lung cancers.
Published in Cell Metabolism, the research centers on the function of glycogen accumulation in the nucleus of a cell. Glycogen is known as a carbohydrate energy storage molecule for cells. Its presence was first described in the nucleus in the 1890s, but no functional role had been described for nuclear glycogen – unlike glycogen stored by the liver or muscle tissue, which is used as a form of energy in various parts of the body.
Scientists from the UK Department of Molecular and Cellular Biochemistry, led by Ramon Sun, PhD, and Matthew S. Gentry, PhD, have discovered that human non-small cell lung cancers accumulate nuclear glycogen during the formation of tumors, providing an opportunity to finally reveal the biological role of nuclear glycogen.
“Nuclear glycogen was first reported in the 1890s and its role in cellular metabolism and impact on disease has been elusive,” Sun says in a statement. “Glycogen is a storage molecule for fuel reserve, but this study demonstrates other functions of glycogen metabolism including epigenetics. Our team demonstrated that nuclear glycogen metabolism modulates the regulatory components of gene expression that are necessary for cancer progression.”
While nuclear glycogen accumulation has been reported in multiple cancers, this study demonstrates that glycogen is synthesized and broken down in the nucleus, that nuclear breakdown provides the fuel for histone modifications, and that these modifications allow cells to become cancerous. Non-small cell lung cancers suppress nuclear glycogen breakdown by decreasing the amount of a key signaling molecule called malin to drive cancer progression.
“We developed a novel nuclear-specific tracer technology coupled to high-resolution mass spectrometry to trace nuclear glycogen metabolism and discovered that it modulates histone acetylation,” Sun says. “We then identified the key signaling events that regulate this newly described cellular process and demonstrated its importance in pre-clinical lung cancer models.”