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Wearing down proteins: How starving cancer cells switch food sources

Breaking down proteins: How starving cancer cells switch food sources
Human cancer cells (cell nucleus in blue) feeding on protein (Albumin, labeled in green). The proteins are digested and divided into proteins in the lysosomes (magenta). Credit: W. Palm / DKFZ

Cancer cells often grow in environments which are lower in nutrients, plus they deal with this challenge by switching their metabolism to using proteins as alternative “food”. Building on genetic screens, a global team of scientists could identify the protein LYSET within a pathway which allows cancer cells to create this switch. Their findings are actually published in the journal Science.

Proteins are the blocks of proteins and key nutrients for and proliferation. Focusing on how cells utilize in is really a central question in basic biology and . Tumor tissues frequently have a limited blood circulation, also to grow under such conditions, switch their metabolic activities. Specifically, they switch from taking on nutrients delivered by arteries to exploiting alternative nutrients, such as for example wearing down surrounding proteins as a food source when facing starvation. However, the mechanisms that enable cancer cells to create this switch have remained largely elusive.

To raised understand the that underlie this nutrient switch in cancer, two sets of scientists with matching expertise teamed up: Wilhelm Palm of the German Cancer Research Center (DKFZ) in Heidelberg is really a leading expert in cancer metabolism, Johannes Zuber at the study Institute of Molecular Pathology (IMP) in Vienna earned ample experience in functional cancer genetics. The scientists create their study with tightly controlled nutrient conditions to mimic amino acid starvation since it occurs in lots of tumors. They used the “gene scissors” CRISPR-Cas9 to disrupt the expression of nearly every gene in the genome, which allowed them to pin down several pathways mixed up in nutrient switch.

Included in this, the scientists spotted an uncharacterized gene that has been only necessary for cell survival when cancer cells were feeding on extracellular proteins. This gene, that your scientists re-named “LYSET” (Lysosomal Enzyme Trafficking Factor), ended up being critical for the event of lysosomes, small organelles that function as stomach of cells where proteins are digested. Further experiments in to the function of LYSET revealed that the gene acts as a core element of the so-called mannose-6-phosphate pathway, that is necessary for filling lysosomes with digestive enzymes. In the lack of LYSET, cancer cells lack enzymes within their lysosomes and so are no longer in a position to digest proteins.

Then your scientists considered mouse models to review the event of LYSET in real tumors. They discovered that the increased loss of LYSET strongly impaired tumor development in a number of forms of cancer, although it was well-tolerated under normal nutrient conditions.

Wilhelm Palm, whose lab was one of the primary who described the power of cancer cells to prey on extracellular proteins, says that “with LYSET, we’ve discovered a central element of a metabolic pathway that allows adaptations to different nutrients, an integral ability of cancer cells to survive and grow in austere Tumor environments.”

“This is exactly what made the discovery so exciting,” says Johannes Zuber. “LYSET and the mannose-6-phosphate pathway grow to be particularly very important to cancer cells and may therefore be considered a molecular entry way for attacking a significant metabolic bottleneck in cancer.”



More info: Catarina Pechincha et al, Lysosomal enzyme trafficking factor LYSET enables nutritional using extracellular proteins, Science (2022). DOI: 10.1126/science.abn5637

Citation: Wearing down proteins: How starving cancer cells switch food sources (2022, September 9) retrieved 9 September 2022 from https://medicalxpress.com/news/2022-09-proteins-starving-cancer-cells-food.html

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