“During chemotherapy or radiation therapy that kills cancer cells by inducing significant DNA damage in their genomes, one of the main side effects for human cancer patients is the depletion of their own adult stem cells, particularly the ones responsible for making new blood and intestine cells. So these patients become anemic, lose appetite and a lot of weight,” said Yang Xu, a professor of biology at UC San Diego who headed the team that published its findings in this week’s advance online issue of the journal Nature Cell Biology. “If we can prevent the loss of stem cells during cancer therapy, that would be very beneficial for these patients.”
Scientists have long known that when normal cells accumulate significant amount of DNA damage, such as during cancer therapy, the tumor suppressor p53 is activated, which leads cells to stop dividing, go into hibernation and undergo a programmed cell death called apoptosis. They’ve also known that a gene called Puma, an acronym for “p53-unregulated modulator of apoptosis,” is critical for p53 to initiate the cell death of DNA-damaged cells.
Using genetically modified mice with persistently activated p53, Xu and his colleagues discovered that, once activated, p53 depletes various adult stem cells, including the ones that are responsible for generating new blood and intestine cells. In addition, Puma is critical for this p53-dependent depletion of various adult stem cells.
“Since p53 is a critical tumor suppressor, you cannot suppress p53 to prevent the depletion of adult stem cells since it will induce cancer,” said Xu. “But you can target Puma to prevent p53-mediated depletion of adult stem cells, because a Puma deficiency does not promote the development of cancer. This gives us a nice target for preventing the p53-dependent depletion of adult stem cells in response to DNA damage. If you can suppress Puma function, you can rescue a lot of the adult stem cells that would otherwise be lost after the accumulation of DNA damage such as during cancer therapy.”
Other co-authors of this paper are Dongping Liu, Linda Ou, Connie Chao and Marshall Lutske of UCSD; Gregory Clemenson and Fred Gage of the Salk Institute for Biological Studies and Gerard Zambetti of St. Jude Children’s Research Hospital in Memphis, Tenn. Funding for the study was provided by the National Institutes of Health.Media Contact:
Kim McDonald | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences