Navigation Links
Split decision: Stem cell signal linked with cancer growth
Date:2/2/2014

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.

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."


'/>"/>

Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

Related biology news :

1. An improved, cost-effective catalyst for water-splitting devices
2. Synthetic molecule first electricity-making catalyst to use iron to split hydrogen gas
3. Vilcek Prize for Biomedical Science split between 2 giants of immunology
4. Bats split on family living
5. UCSB scientists report new beginning in split-brain research, using new analytical tools
6. ATP splitting in membrane protein dynamically measured for the first time
7. Where we split from sharks: Common ancestor comes into focus
8. Low-cost nanosheet catalyst discovered to split hydrogen from water
9. Scientists study the catalytic reactions used by plants to split oxygen from water
10. Designer proteins provide new information about the bodys signal processes
11. FASEB announces 2014 SRC: Phospholipid Cell Signaling & Metabolism in Inflammation & Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Split decision: Stem cell signal linked with cancer growth
(Date:1/20/2016)... Jan. 20, 2016  Synaptics Incorporated (NASDAQ: ... solutions, today announced sampling of S1423, its newest ... and small screen applications including smartwatches, fitness trackers, ... round and rectangular shapes, as well as thick ... with moisture on screen, while wearing gloves, and ...
(Date:1/13/2016)... New York , January 13, 2016 ... Market Research has published a new market report titled ... Growth, Trends, and Forecast, 2015 - 2023. According to the ... in 2014 and is anticipated to reach US$1,625.8 mn ... 2015 to 2023. In terms of volume, the biometric ...
(Date:1/11/2016)... , Jan. 11, 2016  higi, the leading ... 10,000 retail locations, web and mobile, today announced ... million from existing investors. --> ... devoted to further innovate higi,s health platform – ... web portal – including expanding services and programs ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... EDISON, N.J. , Feb. 4, 2016 ... company focused on the development and commercialization of targeted ... BIO CEO & Investor Conference 2016, to be held ... and Source Capital Group,s 2016 Disruptive Growth & Healthcare ... on February 10-11, 2016. James Sapirstein ...
(Date:2/4/2016)... , February 4, 2016 ... Laboratories (ABL), Inc. --> Strasbourg, France ... --> PharmaVentures is pleased to announce that it ... its biopharmaceutical manufacturing unit in Strasbourg, France ... --> --> Transgene (Euronext: ...
(Date:2/3/2016)... -- With the growing need for better therapeutics, and ... such as monoclonal antibodies, recombinant protein therapeutics and ... are in high demand. Conventionally expression systems were ... of these therapeutics. However, due to issues with ... approaches and novel expression systems are currently being ...
(Date:2/3/2016)... ... February 03, 2016 , ... ... a new office dedicated to the North American healthcare market. , Aerocom Healthcare, ... healthcare facilities. The company will provide new pneumatic tube systems or expand ...
Breaking Biology Technology: