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Lung cancer: “Self protection” of tumour cells can be blocked

(Vienna 06-02-2014) During chemotherapy, autophagy helps tumour cells to survive longer, wherein they switch to a so-called energy-saving mode to protect themselves. Researchers of the Klinisches Institut für Pathologie of the MedUni Vienna and of the Institut für Molekulare Biotechnologie (IMBA) [Institute of Molecular Biotechnology] of the Österreichischen Akademie der Wissenschaften (ÖAW) [Austrian Academy of Sciences] have identified a gene that plays a role in this self-protection of the cells in lung cancer. It was also revealed that the removal of this gene results in a blockage of the autophagy, which also enables a considerably longer survival in case of lung cancer. The paper has now been published in the top journal “Nature Communications”.

Autophagy is a “recycling programme” of the cells. During this process, endogenous proteins are digested and reused, among other things. The cell “itself first partly eats into these”. This particularly takes place in stressful situations and if the supply of nutrients is insufficient. This mechanism helps the cell stay alive even when the energy supply is low and ensures the survival of cancel cells in rapidly growing tumours.

In cancer, autophagy plays a dual role: on the one hand, it offers a protective function to limit the tumour necrosis and inflammation, and on the other, it alleviates damage to the genomes in the tumour cells as a reaction to metabolic stress.

In an animal model, the researchers found out that the autophagy controlled by Gen Atg5 plays a significant role in the progression of lung cancer. If this gene is removed, this life-saving energy-saving mode of the cells is blocked, thereby leading to the fact that the survival period increases considerably. In this situation, chemotherapy could work considerably better.

“The aim is to find substances that could block this autophagy. The clinical studies could start after that”, says Lukas Kenner from the Klinisches Institut für Pathologie of the MedUni Vienna and from the Ludwig-Boltzmann-Institut für Krebsforschung. Josef Penninger, Director at IMBA and last author of the study, adds: “Our data shows that one can possibly start with the process of autophagy during the tumour therapy. However, we have also discovered that stopping autophagy in early tumours leads to the fact that actually more cells get transformed into lung cancer cells. Thus, autophagy plays a dual role in the development of cancer. Shuan Rao, postdoc in my group, has also discovered that the role of autophagy in our lung cancer model depends on other tumour suppressors, especially p53”. Further studies for the investigation of these relations are expected to follow.

Highest mortality in lung cancer
Lung cancer is the most common type of cancer. Approximately 20,000 people die every year of cancer in Austria, out of which about 3,600 suffer from lung cancer. The largest risk factor for lung cancer is smoking. Expert: “Even after just ten cigarettes, a genetic symbol of tobacco can be seen.” Additional risks: fine dust, passive smoking, professions in the heavy industry (asbestos, dust, vapours, etc.), heredity and diet. “Studies have shown that adequate consumption of antioxidants such as fruits and vegetables can reduce the risk of cancer”, said the MedUni Vienna researcher.

Service: Nature Communications
“A dual role for autography in a murine model of lung cancer.” Shuan Rao, Luigi Tortola, Thomas Perlot, Gerald Wirnsberger, Maria Novatchkova, Roberto Nitsch, Peter Sykacek, Lukas Frank, Daniel Schramek, Vukoslav Komnenovic, Verena Sigl, Karin Aumayr, Gerald Schmauss, Nicole Fellner, Stephan Handschuh, Martin Glösmann, Pawel Pasierbek, Michaela Schlederer, Guenter P. Resch, Yuting Ma, Heng Yang, Helmuth Popper, Lukas Kenner, Guido Kroemer & Josef M. Penninger. Nature Communications, 20 Jan. 2014. DOI: 10.1038/ncomms4056.