Lactate plays vital role in cancer development

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Researchers are working hard to understand the mechanism responsible for oncogenesis, the process through which normal cells become cancerous ones. A new study focuses on lactate – a molecule produced during intense exercise – and explains its role in cancer cell formation.

New research, published in the journal Carcinogenesis, analyses the role of lactate in oncogenesis.

Lactate is a byproduct of the chemical process known as glycolysis – the breaking down of sugar, or glucose, into smaller molecules with the purpose of producing energy. During intense physical activity, lactate accumulates in the tissue and blood, which can sometimes lead to poorer physical performance and muscle stiffness.

At the beginning of the 20th century, German scientist Otto Warburg noticed that cancer cells consume a lot more glucose than normal cells. The so-called Warburg effect refers to the fact that cancer cells undergo more glycolysis and produce more lactate compared with normal cells.

The new research – led by Inigo San Millan, director of the Sports Performance Department and physiology laboratory at the University of Colorado-Boulder’s Sports Medicine and Performance Center – set out to understand why the Warburg effect happens. Since Warburg’s time, the focus in cancer research has shifted from cell metabolism to genetics, but the new paper hopes to put lactate back at the centre of cancer research.

San Millan and colleagues suggest that the molecule is “the only metabolic compound involved and necessary” in the five stages that follow on from carcinogenesis.

The study examines the role of lactate in angiogenesis (the process by which new blood vessels form inside the tumours), immune escape (the cancer cells’ ability to elude the body’s immune response), and cell migration, as well as in metastasis and self-sufficient metabolism.

The paper explains how in metastasis, lactate helps to create an acidic microenvironment outside the cancer cell, which supports the spread of cancer cells.

Finally, the study also explores the link between lactate and genetic components. The researchers hypothesise that a triad of transcription factors commonly found in most cancers – HIF-1, cMYC, and p53 – also triggers and perpetuates lactate deregulation.

The crucial role of lactate in cancer cell formation may explain why people who exercise regularly are at a lower risk of developing cancer. In athletes and those who work out, the body is trained to efficiently turn lactate into an energy source for the body, thus stopping it from accumulating in excess.

Based on their findings, the researchers speculate that a sedentary lifestyle, combined with too much sugar in our diets, may lead to an excessive accumulation of lactate, thus setting the stage for cancer.