An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled in Switzerland. Hepatocellular carcinoma is usually diagnosed at a very late stage when the liver is already severely damaged and hence overall prognosis is poor. Detection of the anti-cancer protein LHPP as a biomarker may allow clinicians to provide better treatment options.
New anti-cancer protein LHPP
Liver tumors develop from mutated cells that grow and proliferate uncontrollably. Anti-cancer proteins, so-called tumor suppressors, prevent uncontrolled cell growth. Tumor suppressors are often defective in cancer cells. The researchers led by Prof. Michael N. Hall, Biozentrum of the University of Basel, have now discovered a new, so far unknown tumor suppressor, the protein LHPP. In their study, they show that the loss of LHPP promotes tumor growth and reduces the chance of survival of cancer patients. LHPP could potentially be used as a prognostic biomarker.
The researchers generated a mouse model for hepatocellular carcinoma by activating mTOR signaling specifically in the liver. They analyzed a total of more than 4,000 proteins, comparing them in healthy and tumor tissue. An enzyme emerged as the top favorite: the histidine phosphatase LHPP. “It is striking that LHPP is present in healthy tissue and completely absent in tumor tissue,” says first author Sravanth Hindupur. Re-introduction of the genetic information for LHPP by the researchers prevents the formation of tumors and maintains liver function.
Loss of LHPP in cancer patients
“Similar to the mouse model, we also saw a striking decrease in LHPP levels in tumors of patients with liver cancer,” says Hindupur. Additionally, both disease severity and life expectancy correlate with LHPP levels. With complete loss of the tumor suppressor, cancer patients die on average two years earlier. LHPP is useful as a biomarker to classify tumors.
Phosphorylation important for tumorigenesis
LHPP is a phosphatase that removes histidine-linked phosphate groups from proteins. Like all amino acids, histidine is a basic component of proteins. Histidine phosphorylation of proteins has been poorly investigated due to the lack of suitable tools. “Tony Hunter, from the Salk Institute in the USA, has provided us with new tools to analyze histidine phosphorylation. We have now been able to visualize a whole new layer of complexity in tumor formation,” says Hindupur.
Due to the absence of LHPP, global protein histidine phosphorylation is increased, which can lead to activation of several important functions and uncontrolled cell proliferation. This absence promotes the growth of tumors via increasing histidine-phosphorylated proteins. The tumor suppressor LHPP may also play a role in the development of other cancers.
Sravanth K. Hindupur, Marco Colombi, Stephen R. Fuhs, Matthias S. Matter, Yakir Guri, Kevin Adam, Marion Cornu, Salvatore Piscuoglio, Charlotte K.Y. Ng, Charles Betz, Dritan Liko, Luca Quagliata, Suzette Moes, Paul Jenoe, Luigi M. Terracciano, Markus H. Heim, Tony Hunter, Michael N. Hall
The protein histidine phosphatase LHPP is a tumor suppressor
Nature (2018), doi: 10.1038/nature26140
Prof. Dr. Michael Hall, University of Basel, Biozentrum, phone: +41 61 207 21 50, email: email@example.com
Dr. Katrin Bühler, University of Basel, Biozentrum, Communications, phone +41 61 207 09 74, email: firstname.lastname@example.org
Cornelia Niggli | Universität Basel
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