MIT team spotlights role of amino acids in building tumor cells

MIT researchers have found that amino acids contribute more to the building blocks of new cells than glucose does. Since the bulk of the raw cellular mass was traditionally thought to have come from glucose, this new research may have implications in how we think of the molecules that make up cells--including how we can use this information to target cancer growth.

Matthew Vander Heiden, the senior author of the study, heads up the work with his team at Massachusetts Institute of Technology (MIT), and they published in the journal Developmental Cell earlier this month.

"If you want to successfully target cancer metabolism, you need to understand something about how different pathways are being used to actually make mass," said Vander Heiden in a release.

The "Warburg effect" was penned in the 1920s to describe how cancer cells switch to a less efficient metabolism strategy called fermentation, a process that doesn't require oxygen and produces less energy.

It was thought that cancer adopts this strategy to create the building blocks for new cells. One of the criticisms to this idea is that the fermentation of glucose produces lactate--considered a waste product--which is not useful as a building molecule for the formation of a new cell.

The team grew cell several types of cancer cells and normal cells on a petri dish, and they fed the cells with different nutrients with the carbon and nitrogen molecules tagged so they could follow where they ended up. They further calculated the cell mass change after each nutrient was given to the cell.

They first found what was already known; glucose and a small amino acid called glutamine were consumed at a very high amount. However, both molecules did not contribute substantially in the mass of new cells. Glucose contributed 10% to 15%, while glutamine contributed 10% in the carbon composition found in the new cells. The largest contributors to cell mass were amino acids making up a majority 20% to 40% of the total cell mass from any building block material.

"There's some economy in utilizing the simpler, more direct route to build what you're made out of," Vander Heiden said. "If you want to build a house out of bricks, it's easier if you have a pile of bricks around and use those bricks than to start with mud and make new bricks," acknowledging the logic in their finding.

Squaring up to the question of why human cells consume so much glucose when they are dividing when most of it is excreted as lactate, Vander Heiden says, "It refocuses the question. … It isn't necessarily about how the Warburg effect helps cells put glucose into cell mass, but more about why does glucose-to-lactate conversion help cells use amino acids to build more cells."

Vander Heiden's lab will continuing working on a better understanding of how the Warburg effect may help cells to form the cellular material for new cells, including cancer cell growth.

- here's the release
- get the journal abstract

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