Protein-eating cancer cells can be made to starve themselves, research is showing
Scientists from the German Cancer Research Center (DKFZ) in Heidelberg and the Research Institute of Molecular Pathology (IMP) in Vienna have joined forces to try to understand what causes cancer cells to survive so efficiently by eating protein, according to a press release published Friday. The work could open new doors to treating cancer by starving its cells.
A tricky nutrient switch
“Amino acids are the building blocks of proteins and key nutrients for cell growth and proliferation. Understanding how cells utilize amino acids in different environments is a central question in basic biology and cancer research. Tumor tissues often have a limited blood supply, and to grow under such conditions, cancer cells switch their metabolic activities,” stated the press release.
“In particular, they switch from taking up nutrients delivered by blood vessels to exploiting alternative nutrients, such as breaking down surrounding proteins as a food source when facing starvation. However, the mechanisms that enable cancer cells to make this switch have remained largely elusive.”
To get a grasp on how this nutrient switch in cancer works, Wilhelm Palm of DKFZ, a leading expert in cancer metabolism, teamed up with Johannes Zuber of IMP, a specialist in functional cancer genetics. Together, they set up their study with tightly controlled nutrient conditions to mimic amino acid starvation as it occurs in many tumors and used CRISPR-Cas9 to identify several pathways involved in the nutrient switch.
This is how they spotted an uncharacterized gene that was only required for cell survival when cancer cells were feeding on extracellular proteins. The scientists re-named the gene LYSET (Lysosomal Enzyme Trafficking Factor) and explained that it is critical for the function of lysosomes, small organelles that function as the stomach of cells where proteins are digested.
Further experiments undertaken
Further experiments found that, in the absence of LYSET, cancer cells lack enzymes in their lysosomes and are no longer able to digest proteins. To confirm their theories, the scientists then used mouse models to study the function of LYSET in real tumors. They further discovered that the loss of LYSET strongly impaired tumor development in several types of cancer.
"With LYSET, we have discovered a central component of a metabolic pathway that enables adaptations to different nutrients, a key ability of cancer cells to survive and grow in austere tumor environments,” said Palm.
"This is what made the discovery so exciting," added Zuber. "LYSET and the mannose-6-phosphate pathway turn out to be particularly important for cancer cells and could therefore be a molecular entry point for attacking a major metabolic bottleneck in cancer."
What does this mean? By pinpointing the system that helps cancer feed the hope is that it could also be triggered to starve leading to a new and perhaps improved pathway to treating the disease. Researchers have been studying ways to treat cancer for many years but the disease still seems to prevail with many cases reported each year. Could this be the development that finally stops cancer in its tracks?
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