This new stem cell population, reported March 30 in the journal Cell, appears to be relatively quiescent (inactive) – in contrast to the recent discovery of intestinal stem cells that multiply rapidly – and is marked by a protein, Lrig1, that may act as a “brake” on cell growth and proliferation.
The researchers have also developed a new and clinically relevant mouse model of colorectal cancer that investigators can now use to better understand where and how the disease arises, as well as for probing new therapeutic targets.Colorectal cancer is the second leading cause of cancer deaths in the United States. These tumors are thought to arise from a series of mutations in intestinal stem cells, which are long-lived, self-renewing cells that gives rise to all cell types in the intestinal tract.
Those findings “really changed the way we think about intestinal stem cells,” said Robert Coffey, Jr., M.D., Ingram Professor of Cancer Research, co-chair of Vanderbilt’s Epithelial Biology Center and senior author on the study.
“It came to so dominate the field that it raised the question about whether quiescent stem cells even exist…and that’s where we enter into the picture.”Coffey’s lab studies the epidermal growth factor (EGF) signaling pathway – which includes a family of receptors known as ErbBs – and its role in cancers of epithelial tissues, like the intestinal tract.
“Essentially, what we show is that the Lrig1-expressing cells are stem cells and they are largely quiescent,” Powell said. “We also show that they’re distinct from the Lgr5-expressing stem cells that had become a sort of ‘hallmark’ stem cell population…with different gene expression profiles and different proliferative status.”They also showed that Lrig1 is not only a marker of intestinal stem cells, but also acts as a tumor suppressor and inhibits the growth and proliferative signals of the ErbB family – acting as a sort of “brake” on cell proliferation that can lead to cancer.
Postdoctoral fellow Yang Wang, Ph.D., eliminated Lrig1 in mice and showed that nearly all of those mice developed intestinal tumors, providing further evidence suggesting that Lrig1 functions as a tumor suppressor.
The findings underscore the importance of ErbB signaling in the behavior of intestinal stem cells from which colorectal cancer may arise.
Most exciting, said Coffey, is that the mouse model his lab has generated as a part of these studies is one of the only mouse models to develop tumors in section of the intestines where most human tumors develop: the colon. One additional advantage of this model, in contrast to others, is that the tumors develop quickly and can be easily monitored with endoscopy, which will make it easier to assess how therapeutic interventions are working.
“We are fairly confident that this will be the ‘go-to’ model to study colon cancer in mice for the foreseeable future,” Coffey said.
Emily Poulin, Jim Higginbotham, Ph.D., and Jeff Franklin, Ph.D., (from the Coffey lab), Kay Washington, M.D., Ph.D., and Yu Shyr, Ph.D., contributed to the research.
The work was funded by grants from the National Cancer Institute and the National Institute of General Medical Sciences of the National Institutes of Health.
Craig Boerner | Newswise Science News
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences