Altering the architecture of malignant cells may slow spread of cancer
Posted December 15, 2009
COLLEGE STATION, Texas - Cancer may spread throughout the human
body when malignant cells travel in the blood stream. But it may be
possible to slow or even stop those cells from spreading by
altering their structure, according to a recent investigation led
by a Texas A&M University researcher.
The team - assembled by Gonzalo Rivera, an assistant professor
in the Department of Veterinary Pathobiology in the Texas A&M
University College of Veterinary Medicine & Biomedical
Sciences, and scientists from The University of Connecticut Health
Center and the University of California, San Francisco - published
its findings recently in Molecular Cell, a peer-reviewed scientific
The spread of cancer is one example of what can happen when
things go awry with the cytoskeleton, a meshwork created by the
assembly of multiple copies of a cellular protein called actin,
The actin cytoskeleton determines a cell's shape and its ability
to stick to other cells or to tissue. The cytoskeleton is
constantly being reshaped in response to external clues sensed by
cells. Through a complex process of "signal transduction" cells
translate external clues into specific behaviors. They may grow
rapidly. They may alter their functions. Or they may migrate to
others parts of the body.
Cells respond to signals from the environment by several ways.
Among the most critical are the changes in lipids called
phosphoinositides as well as in tyrosine phosphorylation, the
addition of a phosphate group to specific cellular proteins.
"The long-term goal of our research is to define how signals
that alter the cytoskeletal architecture promote cancer initiation
and progression, as well as migration of vascular cells, "Rivera
said. "Our recent article published in Molecular Cell addresses the
important question of how signal transduction mechanisms set in
motion by external clues result in remodeling of the actin
Using a unique combination of experimental approaches, including
molecular genetics, proteomics, and high resolution optical
microscopy, Rivera and his co-investigators uncovered a novel
molecular mechanism in the regulation of N-WASp, a protein
critically involved in rearrangements of the actin
N-WASp is a direct cousin of WASp (Wiskott-Aldrich Syndrome
protein), a protein named after the physicians that first reported
a rare inherited disorder characterized by low level of blood
platelets, eczema, recurrent infections, and a high risk of
leukemia or lymph node tumors in boys.
"Specifically, we demonstrated that a cross-talk between signals
that alter tyrosine phosphorylation and the metabolism of
phosphoinositides is critical in the regulation of N-WASp activity
and the reshaping of the actin meshwork," Rivera said.
"Importantly, our work shows that an 'adaptor protein' termed Nck
is essential in the coupling of phosphotyrosine- and
phosphoinositide-dependent signals that drive cytoskeletal
rearrangements through the N-WASp pathway."
Experimental evidence suggests that reducing Nck levels in
malignant tumor cells drastically diminishes their ability to
migrate in an artificial environment, Rivera explained.
"One could speculate that targeting the intracellular machinery
that modulates actin remodeling, and particularly the N-WASp
signaling hub, may open new avenues for the treatment of invasive
carcinomas," Rivera said. "We are currently determining the role of
this signaling pathway in cytoskeletal changes linked to tumor
formation and metastatic growth."
The article, "Reciprocal Interdependence between Nck and
PI(4,5)P2 Promotes Localized N-WASp-Mediated Actin Polymerization
in Living Cells," can be found in the Nov. 13, 2009, issue of
Angela G. Clendenin
Director, Communications & Public Relations
Ofc - (979) 862-2675
Cell - (979) 739-5718
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