A recent study conducted by the German Cancer Research Center (DKFZ) and the Institute of Molecular Pathology has shed light on a crucial aspect of pancreatic cancer survival. The research team uncovered that the acidic pH levels within tumors, known as acidosis, play a pivotal role in how pancreatic cancer cells adapt their energy metabolism to endure the adverse conditions present in the tumor microenvironment.
Tumors, characterized by oxygen deprivation, nutrient scarcity, and the accumulation of harmful metabolic byproducts, create a hostile environment for cancer cells. Acidosis, a consequence of these conditions, is a key factor influencing cancer cell adaptation to survive in such harsh settings.
Wilhelm Palm and Johannes Zuber, leading the research team, employed the CRISPR-Cas9 gene editing tool to systematically deactivate individual genes in pancreatic cancer cells. Through this approach, they identified genes crucial for cancer cell survival and growth under stressful conditions. Subsequent experiments in mice with pancreatic cancer corroborated the findings from the cell culture studies.
The team’s comprehensive analysis revealed that tumor acidosis significantly impacts the energy metabolism of cancer cells. Under acidic conditions, cancer cells shift from glycolysis to mitochondrial respiration for energy production, a more efficient process. Acidosis induces structural changes in mitochondria, enhancing their efficiency by forming extensive networks, unlike the fragmented structures found in normal cancer cells.
Furthermore, the researchers discovered that acidosis inhibits the activity of the signaling protein ERK, preventing excessive mitochondrial fragmentation. This inhibition allows mitochondria to utilize nutrients more effectively for energy production. When this fusion process is disrupted, cancer cells lose metabolic flexibility, impeding their growth in the acidic tumor environment.
Johannes Zuber emphasized that acidosis serves as a critical switch controlling cancer cell energy supply and survival strategies. These findings offer potential avenues for developing targeted therapies that disrupt tumor energy metabolism, presenting new opportunities for combating pancreatic cancer.
In conclusion, the study underscores the pivotal role of acidic conditions in shaping the energy metabolism of pancreatic cancer cells. By unraveling the mechanisms through which acidosis influences cancer cell survival strategies, the research paves the way for innovative therapeutic approaches targeting tumor energy metabolism.
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