Science: How do hungry cancer cells convert "food" sources when breaking down protein for energy?

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Cancer cells usually grow

However, a growing number of studies have found that non-glucose nutrients such as amino acids, lactic acid, acetic acid, and macromolecules are also being used as alternative energy

On September 8, 2022, an international research team led by Wilhelm Palm of the German Cancer Research Center and Johannes Zuber of the Institute of Molecular Pathology in Vienna, Austria, published a report titled "Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular.

Cancer cells typically grow in environments with low nutrient content, and they address this challenge

Human cancer cells that feed on proteins (green markers) (blue is the nucleus of cancer cells), proteins are digested in lysosomes and broken down into amino acids (magenta)

Amino acids are the building blocks of proteins and are key nutrients

Wilhelm Palm was one of the first to describe the ability of

They then chose a type of tumor that was nutrient-deficient, and extracellular proteins were an important source of

Next, they used CRISPR-Cas9 screening techniques to identify several pathways

The team found that when cells feed on albumin, an important selective key gene is the transmembrane protein TMEM251, which the team named LYSET (lysosomal enzyme transporter

LYSET is a small transmembrane protein containing 131 amino acid residues that lacks significant homology with other proteins

Under nutrient-rich conditions, LYSET is a non-essential gene for cell viability and growth; But in leucine-deficient media with 3% albumin, the deletion of LYSET strongly inhibited proliferation and viability

Further experiments on LYSET function have shown that this gene is a core component of the mannose-6-phosphate (M6P) pathway, which is necessary for lysosomal enzyme transport and therefore for lysosomal nutrient production

Finally, the researchers used a mouse model to study the function

Johannes Zuber (left), Wilhelm Palm (right)

Wilhelm Palm said that by identifying LYSET, a core ingredient

Johannes Zuber said the findings reveal the basic functions of the LYSET and M6P pathways on cells that rely on lysosomal catabolism to produce nutrients, and demonstrate that the pathway is particularly important

Original Source:

Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins.
Science， 2022.