Pancreatic cancer: New approach to treatment discovered?

Reprogrammed mitochondria help cancer cells with oxygen deficiency As tiny power plants of the cells, the so-called mitochondria are usually dependent on oxygen, which they “burn” and thereby provide energy to the body. If the oxygen is missing, the mitochondria can adapt. For example, tumors of the pancreas also make use of this to grow. However, this is also a potential target for the treatment of pancreatic cancer, according to a recent study by the Max Planck Institute for Biology of Aging. “Mitochondria burn oxygen and thereby provide energy for the body,” explain the researchers in a press release of the Max Planck Society on the study results. However, if there is a lack of oxygen and nutrients, the cells must quickly change their energy supply. According to the current study, this is done by reprogramming the mitochondria. “Even tumors of the pancreas use this reprogramming, and can continue to spread despite little existing nutrients and lack of oxygen,” the researchers continue. The underlying signaling pathway therefore provides a good target for pancreatic cancer therapies. Mitochondria switch to glycolysis Previous studies have already shown that cells adapt to oxygen deficiency “by switching their energy supply to so-called glycolysis, in which sugar is fermented without oxygen,” explains the research team. In the human body, for example, this often becomes necessary in old age as the cells are poorly supplied with oxygen and nutrients. “It has been known for some time that cells reduce the number of mitochondria if they change to glycolysis in the absence of oxygen and no longer need it for energy production,” says Max Planck Director Professor Dr. med. Thomas Langer. Responsible signal path discovered Researchers have now discovered that the remaining mitochondria are being reprogrammed to meet new requirements for oxygen and nutrient deficiencies. This happens via a newly discovered signal path in the cell. Thus, a protease (YME1L) in the membrane of mitochondria in the switch to glycolysis is activated and then dismantle a variety of proteins in the organelles. Signal path with built-in timer The effect of this protease activation is that new mitochondria can no longer be formed and the remaining mitochondria change their metabolism. However, the process will eventually stop by itself, since the protease begins to degrade itself at high activity, the researchers report. “This signal path not only has a built-in timer, but allows a very fast response to oxygen deficiency,” says Prof. Langer. “Our results identify the mTORC1-LIPIN1-YME1L axis as a regulator of mitochondrial proteostasis at the interface between metabolism and mitochondrial dynamics,” the researchers report in the journal Nature. Tumor growth significantly reduced Since even in tumors that are poorly supplied with blood and in which little oxygen and nutrients reach the cancer cells, the reprogramming of mitochondria ensures the growth of the tumors, blocking the discovered pathway against the cancer cells could be used. This applies, for example, in pancreatic cancer. The researchers have therefore studied on pancreatic cancer cells in the Petri dish, how the tumor growth behaves when they turn off the signal pathway. Tumor growth was significantly reduced as a result, the research team reports. Basis for new treatment approaches The effect has also been confirmed for tumors in the pancreas of mice, according to the statement of the Max Planck Society. “There is no treatment for pancreatic cancer yet. I believe that this protease can be a very interesting therapeutic target, as we have seen that the signaling pathway is also active in patients with pancreatic cancer, “says Professor Langer. So far, however, no substances are known that act on this protease. (Fp) Author: Dipl. Geogr. Fabian Peters Sources: Max Planck Society: Oxygen deficiency programs mitochondria around (published 06. 11. 2019), mpg.deThomas MacVicar, Yohsuke Ohba, Hendrik Nolte Fiona Carola Mayer, Takashi Tatsuta, Hans-Georg Sprenger, Barbara Lindner, Yue Zhao, Jiahui Li, Christiane Bruns, Marcus Kruger, Markus Habich, Jan Riemer, Robin Schwarzer, Manolis Pasparakis, Sinika Henschke, Jens C. Brüning, Nicola Zamboni , Thomas Langer: Lipid signaling drives proteolytic rewiring of mitochondria by YME1L; in: Nature (published 06. 11. 2019),
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