"Malignant cancer arises when cancer cells acquire the ability to move away from their primary tissue location," said Natalia Starostina assistant research scientist in the UGA department of cellular biology and lead author of the research. "The control of cell movement is a fundamental aspect of animal development, and defects in cell movements can have devastating results ranging from tumor metastasis to vascular disease."
The movement of cells requires the "remodeling" of a supporting cell structure called the actin cytoskeleton. Starostina's research focused on how actin remodeling is controlled and how this regulates the movement of cancer cells.
The study was just published in the journal Developmental Cell. In addition to Starostina, other authors include Jennifer Simpliciano, undergraduate student; Michael McGuirk, lab technician; and Edward Kipreos, head of the lab. Cellular biology is a division of biological sciences in the Franklin College of Arts and Sciences.
The research by Kipreos' group focused on an unlikely source to control cell movement, a CKI protein.CKIs were originally identified as inhibitors of the cell cycle that function in the nucleus to prevent cells from dividing. Surprisingly, in the last few years, scientists noticed that certain very aggressive tumor cells had high levels of CKI in the cytoplasm, which is the part of the cell surrounding the nucleus.
Kipreos' team discovered that a protein known as LRR-1 degrades a CKI called p21 specifically in the cytoplasm of human cells. If LRR-1 is inactivated, then p21 accumulates in the cytoplasm, where it induces the remodeling of the actin cytoskeleton and increases cell movement. One unique aspect of this discovery is that LRR-1 only affects p21 levels in the cytoplasm (where p21 regulates the actin cytoskeleton) but not in the nucleus (where p21 inhibits cell division).
"The finding that LRR-1 controls p21 levels only in the cytoplasm was unexpected," said Kipreos, who also is a researcher in the UGA Cancer Center.
The accumulation of p21 in the cytoplasm causes the rearrangement of the actin cytoskeleton so that rod-like filaments made of actin are broken down, and the released actin is relocated to the periphery of cells where it promotes cell movement.
"While it was known that p21 is involved in remodeling the cytoskeleton, nobody had looked at its effects on cell motility," said Kipreos.
Scientists had previously observed that the accumulation of cytoplasmic p21 in a number of human cancers is associated with high tumor grade and poor prognosis. The Kipreos team's research shows that tumor cells with cytoplasmic CKI have increased movement, suggesting the reason these tumor cells are more aggressive is because their enhanced cell movements lead to metastasis in which the cancer spreads through the body.
"This work provides a key insight into how the movement of cells is controlled and explains why cancers with high cytoplasmic CKI levels are so aggressive," said Kipreos.
The team's initial breakthrough in linking LRR-1 to the degradation of CKI came from studying the small roundworm Caenorhabditis elegans. They found that in the worm LRR-1 specifically degrades the nuclear form of CKI to allow cells to divide.
"We thought it was very interesting that in worms, LRR-1 degrades a CKI in the nucleus to regulate cell division, while in humans, it degrades a CKI in the cytoplasm to control cell movement," said Starostina.
Exactly how the new information might be used to develop diagnostics or therapies to treat cancer awaits development. But the discovery of this new regulatory pathway gives researchers a target that could one day allow them to slow the spread of tumors or halt cancer cells in their tracks.
For more information about the UGA department of cellular biology, see http://www.uga.edu/cellbio/. For more information about the UGA Cancer Center, see http://www.uga.edu/cancercenter
Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital
Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences