A team of scientists at the Institut de recherches cliniques de Montréal (IRCM) led by Dr. Jean-François Côté, Director of the Cytoskeletal Organization and Cell Migration research unit, identified a novel molecular mechanism in the control of cell motility.
Their findings were published online today in Current Biology, a journal from the Cell Press group. This scientific breakthrough could eventually lead to the development of new cancer-treating drugs that could block the spread of tumours (metastasis).
"As many as 90% of cancer patient deaths are attributable to metastasis, which explains the importance of understanding the molecular mechanisms at the basis of this harmful process," says Dr. Côté. "This is why, over the past few years, we have focused our research on DOCK180, a protein involved in intracellular signalling networks, and more particularly on the DOCK180/Rac1 signalling pathway, which is suspected to be a key mediator of tumour metastasis."
Unlike normal cells that migrate throughout embryonic and adult life to perform their specialized functions, cancer cells metastasize in order to lethally spread throughout the body. At a molecular level, DOCK180 specifically activates the small Rac1 protein, which, in turn, modifies a cell's shape and promotes cell motility and invasion. Dr. Côté's team had previously demonstrated in detail how DOCK180, with the help of its binding partner ELMO, acts on Rac1 to promote robust cell migration.
"We knew that this signalling pathway had to be regulated to prevent uncontrolled cell migration in normal conditions, but until now, the mechanisms involved had been eluding us and other scientists," explains Manishha Patel, a PhD student in Dr. Côté's laboratory and co-author of the study. "With our recent findings, we demonstrated that the ELMO protein closes in on itself to enter a repressed state, thus preventing the activation of the DOCK180/Rac pathway."
"Our team identified three regions in ELMO that allow it to toggle between a closed/inactive and open/active shape," adds Dr. Yoran Margaron, a postdoctoral fellow in the same research unit and one of the article's co-authors. "We showed that if we disrupt ELMO's regulatory feature and maintain the protein in an open state, we can fully activate the DOCK180/Rac pathway and significantly increase the migration potential of cells."
The researchers' next step is to investigate the regulation of ELMO in cancer cells. Based on their latest findings, they will attempt to maintain ELMO in a repressed state within cancer cells to prevent metastasis, which could have a major impact on the development of potential cancer treatments.
This research project was supported by the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI). Other collaborators for this study include Nadine Fradet, Qi Yang and Brian Wilkes from the IRCM, as well as Dr. Michel Bouvier from the Institut de recherche en immunologie et en cancérologie (IRIC), and Dr. Kay Hoffman from Miltenyi Biotec in Germany.
For more information, please refer to the online article published by Current Biology. The print publication will be available on November 23, 2010.
Julie Langelier | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy