Understanding the Role of Sphingolipids in Cancer Development

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Understanding the Role of Sphingolipids in Cancer Development

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Research Horizons - For almost 30 years, Georgia Tech professor Alfred Merrill has been studying lipids - the fats, oils, cholesterols and certain vitamins that our bodies need to grow and survive. Today, his expertise lies in a subgroup of lipids called sphingolipids, which influence cell structure, signaling and interaction.

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  • Al Merrill :: Photo By Gary Meek Al Merrill :: Photo By Gary Meek
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Research Horizons, July 09 - For almost 30 years, Georgia Tech professor Alfred Merrill has been studying lipids - the fats, oils, cholesterols and certain vitamins that our bodies need to grow and survive. Today, his expertise lies in a subgroup of lipids called sphingolipids, which influence cell structure,

"The lipid backbones of sphingolipids are important cell-signaling molecules that turn on and turn off intracellular proteins that are involved in cell growth, death, and an interesting process called autophagy that has recently gained much attention in the cancer research field," says Merrill, who is also the School of Biology's Smithgall Chair in Molecular Cell Biology.

Autophagy - meaning "self-eating" - involves the degradation of cellular compartments, called organelles, and cellular proteins. During this process, a cell forms a vesicle that encapsulates its cytoplasm and some of the organelles and then fuses with digestive enzymes that degrade the contents of the vesicle and make them available for cell nutrition.

Interestingly, autophagy has been implicated in both cancer cell death and survival. Since Merrill's research has shown that sphingolipid signaling is essential for creating autophagy vesicles, these metabolites may be involved in both promoting and limiting tumor growth.

Autophagy promotes cancer cell survival by allowing cells to respond to changing environmental conditions, such as nutrient deprivation. During starvation, autophagy allows cells to degrade proteins and organelles and thus obtain a source of nutrients that would not be available otherwise.

"Cancer cells use autophagy because as they are developing they have a period in which they go into a nutrient crisis because they haven't established their own blood and nutrient flow, so they use autophagy as a way to survive in the meantime," explains Merrill.

However, this same process of gaining nutrients can lead to tumor cell death as well. Merrill's laboratory found that a number of anti-cancer agents promote the formation of these vesicles through sphingolipid signaling.

"Preliminary data supports the theory that the autophagic vesicles in cancer cells are unstable, so if one of their components-the sphingolipids-is out of balance, this can cause them to break apart and spill out their toxic contents, killing the cancer cell," adds Merrill.

While the mechanism through which autophagy inhibits tumor development is still unclear, graduate student Kacee Sims is examining the role of sphingolipid pathways in the conversion of autophagy from a cancer cell survival pathway to a cell death pathway.

The project described was supported by Award No. U54GM069338 from the National Institute of General Medicine Sciences (NIGMS). Any opinions, findings, conclusions or recommendations expressed are those of the researcher and do not necessarily reflect the views of the NIGMS or the National Institutes of Health. Significant funding to support this research was also provided by the Smithgall Endowment Georgia Tech.

By Abby Vogel
Photo By Gary Meek

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  • Created By: Troy Hilley
  • Workflow Status: Published
  • Created On: Aug 12, 2009 - 8:00pm
  • Last Updated: Oct 7, 2016 - 11:11pm