In the early stages of human embryogenesis, a transcription factor called Twist1 plays a key regulatory role in how the embryo assumes form and function. Much later in life, however, researchers at the University of California, San Diego School of Medicine, say Twist1 can re-emerge, taking a darker and more deadly turn.
In a paper published in the March 15, 2011 issue of Cancer Cell, UCSD scientists led by Jing Yang, PhD, assistant professor of pharmacology and pediatrics, identify a unique function of Twist1 in later life: it promotes the formation of invadopodia in tumor cells, a vital step in the spread of such cells (metastasis) to surrounding tissues and other parts of the body.
Invadopodia (meaning "invasive feet") are tiny protrusions of tumor cells that extend into the extracellular matrix -- the surrounding connective tissue and fibers that provide support. Invadopodia concentrate enzymes that degrade the matrix so that tumor cells can break away and metastasize.
Previous studies have linked the expression of Twist1 to many aggressive, solid-tumor cancers, including melanomas, neuroblastomas, as well as breast and prostate cancer. The new research by Yang and colleagues describes in detail how Twist1 initiates the multi-step pathway resulting in invadopodia formation and matrix degradation. The research also reveals places in the process that may present potential targets for future anti-metastasis therapies.
After embryogenesis, Twist1 is normally suppressed. Cancer cells, however, reactivate the transcription factor, enabling Twist1 to initiate its complex pathway leading to metastasis. Drug designers, however, have yet to successfully devise a way to directly inhibit transcription factors like Twist1. The UCSD study points to other possibilities.
"We hope to inhibit downstream targets of Twist1 (such as platelet-derived growth factor receptors) to inhibit invadopodia formation and function," Yang said. "Our study suggests that inhibition of invadopodia-mediated matrix degradation could be an effective way to suppress metastasis."
If that happens, a cancer tumor becomes a stable, unmoving and easier target for other types of therapeutic treatments.
Co-authors of the paper include Mark A. Eckert and Andrew T. Chang, UCSD Molecular Pathology Graduate Program and Biomedical Science Graduate Program; Thinzar M. Lwin and Etienne Danis, UCSD Department of Pharmacology; and Jihoon Kim and Lucila Ohno-Machado, UCSD Division of Biomedical Informatics.
Research funding came, in part, from the National Institutes of Health, the Sydney Kimmel Foundation for Cancer Research, the California Breast Cancer Research Program and the Susan G. Komen Foundation.
Scott LaFee | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences