Lactate May Prompt Cancer Formation

In a study published yesterday in Frontiers in Oncology, University of Colorado researchers found that a byproduct of glucose called lactate may also prompt a mutated cell to become cancerous. Lactate, which is used by every cell in the body, is not a waste product but a major source of energy for the cell.

“We discovered that lactate is a catalyst that triggers a mechanism in mutated cells necessary to continue the cancer forming process,” says first author Iñigo San Millán. “This opens a new door to better understand cancer at the metabolic level. It also means we might be able to target lactate with new therapies.”

The role of lactate in cancer was first described nearly a century ago when Nobel Laureate Otto Warburg discovered that cancer cells were characterized not only by their high glucose consumption but also by a marked increase in lactate production. The process was called “The Warburg Effect.” But exactly how it worked remained a mystery.

In 2017, San Millán and a colleague published a hypothesis they believe explained the meaning and purpose of the Warburg Effect: to produce lactate for cancer formation. To demonstrate this hypothesis, the team exposed human breast cancer cells to glucose, which then produced lactate. The lactate increased the expression of all the main mutated genes involved in breast cancer between 150–800%.

It’s well known that not every mutated cell becomes cancerous, and there has been speculation on what factors might trigger the expression of mutated genes. This study demonstrates that lactate is a key trigger. Now, the researchers are reproducing this study in other cancers and finding similar results.

“Lactate, which used to be considered a waste product, turns out to be a major signaling molecule and a major regulator of the genes involved in cancer,” says San Millán. “This is not the same behavior of lactate we get from doing exercise because that is quickly removed by the muscles and has positive signaling properties to improve physical fitness. The lactate produced in cancer stays put, is constantly being produced, and acts as a catalyst to activate mutated genes into cancer. We still don’t know these mechanisms but we are investigating them now.”