Cancer cells are often poorly supplied with blood vessels and therefore have to grow in a nutrient-poor environment. They cope by switching to protein as an alternative food source. Scientists in Vienna and Heidelberg have now identified a protein that enables cancer cells to switch to alternative foods, as reported in the journal Science. This could indicate a possible way to starve out cancer cells in a targeted manner.
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Tumor development could be slowed down in mouse models
Preferred foods for cells are usually free amino acids, the building blocks of proteins that are supplied in the blood. When cancer cells in tumor tissue poorly supplied with blood have few nutrients available, they can change their diet and switch to breaking down proteins in their environment. So far, the mechanisms of this switch have not been well understood.
In their work, the scientists led by Johannes Zuber from the Research Institute for Molecular Pathology (IMP) and Wilhelm Palm from the German Cancer Research Center (DKFZ) in Heidelberg exposed cancer cells to an amino acid deficiency that occurs in many tumors. They then used CRISPR-Cas9 gene scissors to turn off genes one at a time to identify components involved in switching the nutrient source.
“LYSET” crucial for lysosomes
The researchers discovered a previously uncharacterized gene that only plays a role when the cancer cells feed on proteins from the environment due to a lack of normal nutrients. This gene, known as “LYSET” (Lysosomal Enzyme Trafficking Factor), is crucial for the function of the so-called lysosomes, which are also known as the “stomach of the cell”. These small cell structures contain, among other things, enzymes to break down foreign substances or endogenous substances such as proteins.
Further experiments indicated that LYSET is a central component of the metabolic pathway (mannose-6-phosphate) that supplies the lysosomes with digestive enzymes. If LYSET is missing, the cancer cells lack the enzymes in their lysosomes and can no longer switch to the alternative nutrient source. In several mouse models, the researchers showed that tumor development is then greatly slowed down. Zuber therefore sees in LYSET and the mannose-6-phosphate pathway a possible molecular starting point to therapeutically intervene in the metabolism of cancer cells, as he explained in a press release.
Publication: http://dx.doi.org/10.1126/science.abn5637
(APA/red, Photo: APA/APA/dpa)