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.
The protein, which a research team from Vienna and Heidelberg has now identified, enables the cancer cells to switch to alternative foods – and this in turn might be a way of starving them out. A study was made on this in the journal “Science” released.
Cancer cells have been subjected to amino acid deprivation
The team around John Zuber from the Research Institute for Molecular Pathology (IMP) in Vienna and Wilhelm Palm from the German Cancer Research Center (DKFZ) in Heidelberg exposed cancer cells to an amino acid deficiency as it 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.
The researchers discovered a previously uncharacterized protein that only plays a role when the cancer cells feed on proteins from the environment due to a lack of usual nutrients: LYSET (lysosomal enzyme trafficking factor) is crucial for the function of the so-called lysosomes, the 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.
Tumor development greatly slowed down
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 LYSET and the mannose-6-phosphate pathway as a possible molecular starting point to therapeutically intervene in the metabolism of cancer cells.
