Why does breast cancer develop and how come certain patients are resistant to established therapies? Researchers from the University of Basel have gained new insights into the molecular processes in breast tissue. They identified the tumor suppressor LATS as a key player in the development and treatment of breast cancer. The journal Nature has published the results today.
All breast cancers are not created equal. In up to 70 percent of all breast cancers, the tumor has receptors for the hormone estrogen. Today, these estrogen-receptor-positive cancers can be treated relatively well. Because these tumors need estrogen for their growth, the receptor is the target of a number of drugs that interfere with estrogen expression, bind to the receptor or speed up its degeneration.
However, around a third of all patients does not react to therapy or develops resistance. So far it has not been possible to accurately predict who will respond to this therapy, because the underlying molecular mechanisms are not yet understood entirely.
In a comprehensive molecular study, a group of scientists led by Prof. Mohamed Bentires-Alj from the Department of Biomedicine at the University and the University Hospital of Basel has now identified an important player in this process named LATS. They were able to show how this enzyme, in cooperation with other proteins, influences the development and treatment of breast cancer.
Tumor suppressor LATS decides cell fate
The researchers focused on cancer-inhibiting genes that prevent normal cells from becoming cancerous. In particular, they studied the tumor suppressors LATS1 and LATS2. Once LATS is deleted, the processes in the breast tissue change.
Without LATS, the number of so-called luminal precursor cells in the epithelial tissue of breast glands increases. These are the cells of origin of most types of breast cancer in humans. “LATS balances cell fate in the breast tissue. In its absence the equilibrium shifts and more cells that can give rise to tumors develop”, explains Bentires-Alj.
Resistance to degradation
In healthy breast tissue, LATS brings together the estrogen receptor alpha with the protein degradation machinery. Without LATS the receptor can no longer be properly degraded, which has consequences for cancer therapy. “We were able to show that cancer cells without LATS no longer respond to Fluvestrant, an estrogen-receptor antagonist that promotes its degradation. They were resistant”, says Bentires-Alj.
The removal of LATS also stabilized the proteins YAP and TAZ, which are upregulated in many cancers and boost cell proliferation. “Thanks to our newly gained insights into the molecular processes in healthy breast tissue, we now also better understand how cells of origin of cancer expand and why certain tumors are resistant to therapy”, summarizes the Basel scientists Bentires-Alj.
Adrian Britschgi, Stephan Duss, Sungeun Kim, Joana P. Couto, Heike Brinkhaus, Shany Koren, Duvini De Silva, Kirsten D. Mertz, Daniela Kaup, Zsuzsanna Varga, Hans Voshol, Alexandra Vissieres, Cedric Leroy, Tim Roloff, Michael B. Stadler, Christina H. Scheel, Loren J. Miraglia, Anthony P. Orth, Ghislain M. C. Bonamy, Venkateshwar A. Reddy & Mohamed Bentires-Alj
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with Erα
Nature (2017), doi: 10.1038/nature20829
Prof. Dr. Mohamed Bentires-Alj, University of Basel / University Hospital Basel, Department of Biomedicine, Phone: +41 61 265 33 13, Email: firstname.lastname@example.org
Olivia Poisson | Universität Basel
Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)
Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital 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