Dartmouth Medical School geneticists have discovered a striking turnabout role for a gatekeeper known to put on the brakes for colon cancer. Flaws in a gene called adenomatous polyposis coli (APC), which normally prevents excessive cell growth, are thought to trigger development of most colorectal cancers.
But in an about face, the tumor suppressor gene also has a second task, the researchers found, as a gas pedal that accelerates signaling between cells. This novel duality is reported in the January 18 issue of Science by a team led by Dr. Yashi Ahmed, assistant professor of genetics at DMS.
“Colon cancer is the second most frequent cause of cancer-related death in the United States,” said Ahmed. “Understanding the normal role of APC and what’s happening to cells that have lost the gene can help us identify therapeutic targets for drug action against this common cancer.”
APC was first identified in families with a hereditary predisposition to develop colon cancer. Family members are born with an error in one of their two APC gene copies, but are fine as long as the other gene copy is normal. However, many of their colon cells develop a second defective gene. As a result, by their teens and twenties these individuals get hundreds to thousands of colon growths--called polyps--some of which invariably progress to cancer, so their colon is usually removed when they are in their twenties.
But these types of polyps that have a strong association with cancer are not limited to hereditary colon cancer. By age 60, according to Ahmed, up to 40 percent of the general population will have at least one such polyp with mutations in both APC genes. Fortunately, with a colonoscopy to view the colon many polyps can be removed in their early stages, before they become cancer.
APC is part of a vital signaling pathway that coordinates cell growth in all animals—from flies through people. During embryonic development, this pathway causes cells to grow and differentiate to become the kind of cells they should be. In many adult cells, however, the pathway should be turned off, and APC puts the brakes on the pathway to stop cell growth.
The researchers devised strategies to explore the molecular workings of APC in the fruit fly, a simple animal with rapid breeding time that offers many advantages in the laboratory. When they remove or reduce APC, they see fruit flies with no wings, peculiar abdomens and many other oddities.
However, APC defects found in colonic polyps have an unusual feature. Generally, gene mutations can disrupt an entire protein, but in colon cancers, only half the APC protein is lost, while the other half remains, Ahmed explains. Her work in fruit flies suggests a reason for this unexplained phenomenon.
“We found that APC has a second, new job. It not only puts the brake on cell signaling, but also gives some gas. These two functions are controlled by different parts of the protein. In the colon cancers, the brake part of the APC protein is lost, but there is strong pressure to retain the give-it-some-gas portion,” Ahmed said.
Indeed, the DMS team’s data suggest that this new “gas” facet is also present in the human APC protein, reinforcing APC’s role as a regulator that promotes or suppresses cell growth. Future studies on how APC balances signals may help benefit treatments not only for colon tumors, but also for birth defects, since the signaling pathway regulated by APC affects nearly all tissues during development.
Hali Wickner | EurekAlert!
Flavins keep a handy helper in their pocket
25.04.2018 | University of Freiburg
Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
25.04.2018 | Physics and Astronomy
25.04.2018 | Physics and Astronomy
25.04.2018 | Information Technology