Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Split decision: Stem cell signal linked with cancer growth

03.02.2014
Researchers at the University of California, San Diego School of Medicine have identified a protein critical to hematopoietic stem cell function and blood formation. The finding has potential as a new target for treating leukemia because cancer stem cells rely upon the same protein to regulate and sustain their growth.

Hematopoietic stem cells give rise to all other blood cells. Writing in the February 2, 2014 advance online issue of Nature Genetics, principal investigator Tannishtha Reya, PhD, professor in the Department of Pharmacology, and colleagues found that a protein called Lis1 fundamentally regulates asymmetric division of hematopoietic stem cells, assuring that the stem cells correctly differentiate to provide an adequate, sustained supply of new blood cells.


This is a confocal micrograph of a human melanoma cell undergoing division or mitosis. The resulting daughter cells are temporarily linked by a bridge of remaining cytoplasm. Green staining labels the endoplasmic reticulum; red colors the mitochondria. Blue indicates the chromosomes.

Credit: Wellcome Images

Asymmetric division occurs when a stem cell divides into two daughter cells of unequal inheritance: One daughter differentiates into a permanently specialized cell type while the other remains undifferentiated and capable of further divisions.

"This process is very important for the proper generation of all the cells needed for the development and function of many normal tissues," said Reya. When cells divide, Lis1 controls orientation of the mitotic spindle, an apparatus of subcellular fibers that segregates chromosomes during cell division.

"During division, the spindle is attached to a particular point on the cell membrane, which also determines the axis along which the cell will divide," Reya said. "Because proteins are not evenly distributed throughout the cell, the axis of division, in turn, determines the types and amounts of proteins that get distributed to each daughter cell. By analogy, imagine the difference between cutting the Earth along the equator versus halving it longitudinally. In each case, the countries that wind up in the two halves are different."

When researchers deleted Lis1 from mouse hematopoietic stem cells, differentiation was radically altered. Asymmetric division increased and accelerated differentiation, resulting in an oversupply of specialized cells and an ever-diminishing reserve of undifferentiated stem cells, which eventually resulted in a bloodless mouse.

"What we found was that a large part of the defect in blood formation was due to a failure of stem cells to expand," said Reya. "Instead of undergoing symmetric divisions to generate two stem cell daughters, they predominantly underwent asymmetric division to generate more specialized cells. As a result, the mice were unable to generate enough stem cells to sustain blood cell production."

The scientists next looked at how cancer stem cells in mice behaved when the Lis1 signaling pathway was blocked, discovering that they too lost the ability to renew and propagate. "In this sense, the effect Lis1 has on leukemic self-renewal parallels its role in normal stem cell self-renewal," Reya said.

Reya said the findings shed new light on the fundamental regulators of cell growth both in normal development and in cancer.

"Our work shows that elimination of Lis1 potently inhibits cancer growth, and identifies Lis1 and other regulators of protein inheritance as a new class of molecules that could be targeted in cancer therapy."

In the long term, Reya noted, it remains to be determined whether inhibiting Lis1 in cancer cells would produce unacceptable consequences in normal cells as well. "A number of commonly used hemotherapy agents target the machinery that controls cell division. Although these agents can be toxic, their effects on cancer cells are much more potent than their effects on normal cells, and so they continue to be used. Agents that target Lis1 might be more specific and less toxic, which would give them significant clinical value."

Co-authors are Bryan Zimdahl, UCSD Department of Pharmacology, Sanford Consortium for Regenerative Medicine and Duke University Medical Center; Takahiro Ito, Jeevisha Bajaj, Takaaki Konuma, Joi Weeks, Claire S. Koechlein, Hyog Young Kwon and Omead Arami, UCSD Department of Pharmacology and Sanford Consortium for Regenerative Medicine; David Rizzieri, Duke University Medical Center; H. Elizabeth Broome, UC San Diego Moores Cancer Center; Charles Chuah, Singapore General Hospital and Duke-National University of Singapore Graduate Medical School; Vivian G. Oehler, Fred Hutchinson Cancer Research Center; Roman Sasik and Gary Hardiman, UCSD Department of Medicine.

Funding support came, in part, from the National Institutes of Health, (grants T32 GM007184-33 and T32 GM007752), the UC San Diego Moores Cancer Center, the California Institute for Regenerative Medicine, the Japanese Society for the Promotion of Science and the Leukemia and Lymphoma Society.

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht New switch decides between genome repair and death of cells
27.09.2016 | University of Cologne - Universität zu Köln

nachricht A blue stoplight to prevent runaway photosynthesis
27.09.2016 | National Institute for Basic Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

 
Latest News

New imaging technique in Alzheimer’s disease - opens up possibilities for new drug development

28.09.2016 | Medical Engineering

Innovate coating extends the life of materials for industrial use

28.09.2016 | Materials Sciences

Blockchain Set to Transform the Financial Services Market

28.09.2016 | Business and Finance

VideoLinks
B2B-VideoLinks
More VideoLinks >>>