Cancer cells in starvation mode: New study reveals surprising cooperation!

New research is examining how cancer cells handle nutrients and how they may be prevented from receiving therapy. Two important studies shed light on the mechanisms by which tumor cells survive in the face of nutrient deficiency.

A study by US and French scientists published in the journal Nature shows that cancer cells cooperate in the distribution of nutrients, particularly amino acids. Previous theories assumed that cancer cells compete for nutrients, resulting in more aggressive tumors. The new study, led by Carlos Carmona-Fontaine of New York University, uses a robotic microscope and specialized image analysis software to analyze the growth of cancer cells under various conditions.

Cooperation among cancer cells

The research results show that cancer cells work together more when there is a lack of amino acids, especially glutamine. While larger cell populations benefit from an amino acid deficiency, smaller cell groups are disadvantaged. Tumor cells release enzymes that break down oligopeptides, small proteins made up of amino acid chains, into free amino acids. This cooperation creates a shared pool of amino acids that is crucial for survival in the tumor microenvironment. It was also tested whether inhibiting a certain enzyme with the drug bestatin could stop tumor growth, which was confirmed in the results. Experimental approaches in which the gene for the enzyme was switched off using the Crispr gene scissors also led to a slowing of tumor growth in mice, especially as part of a protein-restricted diet.

In addition, scientists from the German Cancer Research Center (DKFZ) in Heidelberg and the Research Institute for Molecular Pathology (IMP) in Vienna have again examined the survival mechanisms of cancer cells. They found that when nutrient deficient, cancer cells can switch to alternative food sources, particularly breaking down proteins from their environment. Using the CRISPR-Cas9 gene scissors, the researchers switched off the expression of almost all genes in order to identify genetic components that are involved in this switching process.

The study revealed the discovery of a previously uncharacterized gene that is required for the survival of cancer cells when they obtain their nutrients from extracellular proteins. This gene codes for the membrane protein “LYSET” (Lysosomal Enzyme Trafficking Factor), which plays a central role in the function of lysosomes. Lysosomes are responsible for digesting proteins in the cell. If LYSET is missing, it is not possible for the cancer cells to switch to alternative nutrient sources, which slows tumor development in laboratory animals. The importance of LYSET and the mannose-6-phosphate metabolic pathway could provide future therapeutic targets for combating metabolic bottlenecks in cancer, as reported in the journal “Science”.

In summary, recent research shows that a better understanding of nutrient uptake and interactions between cancer cells could potentially lead to innovative treatment approaches. The findings from the study of nutrient cooperation and genetic factors could open up new strategies in the fight against cancer, especially through the combination of enzyme inhibition and targeted dietary adjustments.