Cells have two different programs to safeguard them from getting out of control and developing cancer. One of them is senescence (biological aging). It puts cancer cells into a permanent sleep so they no longer divide and grow in an uncontrolled way.
Now the research group led by Professor Walter Birchmeier (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch) has discovered that an enzyme known to be active in breast cancer and leukemia blocks this protection program and boosts tumor growth.
They succeeded in blocking this enzyme in mice with breast cancer, thus reactivating senescence and stopping tumor growth (EMBO-Journal, DOI 10.15252/embj.201489004)*.
The enzyme Shp2 belongs to a group of enzymes called tyrosine phosphatases. These enzymes are major cell growth regulators. Shp2, for example, plays an essential role in early embryogenesis and is also known to play a role in cancer.
Some years ago researchers showed that Shp2 is upregulated in 70 percent of invasive breast cancers. These forms of breast cancer are particularly aggressive. Recent studies with human breast cancer cell lines have also shown that Shp2 mediates survival signals in cancer cells.
Reason enough for MDC cancer researcher Professor Birchmeier, who for years has been studying signaling in cancer, to further investigate this enzyme with his research team colleagues Dr. Linxiang Lan and Dr. Jane Holland. Also, current evidence shows that senescence may play an inhibitory role in breast cancer.
The MDC researchers therefore studied mice which carried the breast cancer gene PyMT. This oncogene rapidly initiates breast cancer, which also metastasizes. The researchers noted that the enzyme Shp2 is very active in these mice.
They were able to show that Shp2 initiates a signaling cascade. Within this cascade Shp2 turns on different signaling molecules, but turns off the tumor suppressor genes p27 und p53. As a result, the senescence protection program is also shut off.
The question of interest was whether or not senescence can be turned on again. Is it possible to target Shp2 directly and shut it off? Using a small molecule, researchers of the biotech company Experimental Pharmacology and Oncology (EPO), based on the Berlin-Buch campus as is the MDC, were able to shut down the Shp2 gene in the mice with breast cancer.
In this way they were able to reactivate the senescence program and stop the growth of the breast cancer cells. The small molecule was developed by the Leibniz-Institut für molekulare Pharmakologie (FMP) in Berlin-Buch. However, it is still an experimental drug and has not been licensed for use in human patients.
The next step was to find out which role Shp2 and its target genes play in human patients with breast cancer. Dr. Balázs Györffy of Semmelweiss University in Budapest, Hungary, a longtime collaborator of Professor Birchmeier, looked at the retrospective data of almost 4,000 patients.
After analyzing the data, he and his collaborators in Berlin are convinced that the activity of Shp2 and its target genes can predict the outcome of breast cancer: The less active Shp2 is, the higher the chance for the affected women to stay relapse-free after having undergone a successful breast cancer therapy.
“Our data suggest that senescence induction by inhibiting Shp2 or controlling its targets may be useful in therapeutic approaches to breast cancer,” the researchers conclude. Cancer cells in the senescence mode secrete messenger molecules of the immune system (cytokines), enabling the body’s defense system to identify these sleeping cancer cells and destroy them.
*Shp2 Signaling is Essential to the Suppression of Senescence in PyMT-induced Mammary Gland Cancer in Mice
Linxiang Lan1, Jane D. Holland1, Jingjing Qi1, Stefanie Grosskopf1, Regina Vogel1, Balázs Györffy2,3, Annika Wulf-Goldenberg4, Walter Birchmeier1,*
1 Cancer Research Program, Max Delbrück Center for Molecular Medicine (MDC) Berlin, Germany
2 MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary
3 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
4 Experimental Pharmacology & Oncology (EPO), Berlin, Germany
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
Barbara Bachtler | Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences