When the protein, TCF3, is modified by a small molecule called a phosphate, it no longer binds DNA, changing the way the protein signals during development. This discovery identifies a new diagnostic marker (phosphorylated TCF3) that may be associated with cancer and could represent a potential drug target. The results are published in the current issue of Developmental Cell.
Led by Sergei Sokol, PhD, Professor of Developmental and Regenerative Biology at Mount Sinai School of Medicine, the research team analyzed frog embryos to get a better understanding of how cells "talk" to each other and differentiate into various cell types, e.g., neurons or muscle cells. One such way these cells communicate is through signaling proteins called Wnts, which function during embryonic development and malfunction in cancer, including colon carcinomas, melanomas, skin, lung and liver tumors. Dr. Sokol's team analyzed what happens when a cell responds to Wnt protein..
The researchers' results suggest that Wnt signal activates a special enzyme, called homeodomain-interacting protein kinase that adds a phosphate group to TCF3. This event changes the activity of TCF3 and activates gene expression during early development, allowing embryonic tissues to develop tail structures. Although essential in the early embryo, the same process can cause tumor formation in the adult.
"Our study is the first to show an alternative mechanism of Wnt signaling, that operates in vivo to modulate the activity of TCF3," said Dr. Sokol. "We now know that this change in TCF3 activity leads to a profound alteration of target genes that are important in early development and are abnormally regulated in cancer."
These data potentially provide a diagnostic or therapeutic target in identifying and treating common types of cancer. If the presence of the phosphate molecule on TCF3 is identified, then the cancer may be caught earlier, providing more treatment options. Additionally, knowing that this modification of TCF3 may cause abnormal cell growth would allow researchers to develop drugs that can inhibit its action.
"While more research is needed, our study is a promising first step toward earlier diagnosis and better treatment for many common cancers," said Dr. Sokol. "We look forward to gaining further understanding of the role of TCF regulation for gene expression."
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. U.S. News & World Report consistently ranks The Mount Sinai Hospital among the nation's best hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
For more information, visit www.mountsinai.org. Follow us on Twitter @mountsinainyc.
Mount Sinai Press Office | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences