Discovery of a mechanism that regulates cell movement

July 21, 2008

In Nature Cell Biology, researchers at IRB Barcelona describe a mechanism that governs adhesion between cells and therefore their capacity to move

A study performed by researchers at the Institute for Research in Biomedicine (IRB Barcelona), in collaboration with researchers at the Instituto de Biología Molecular of the CSIC, reveal a mechanism that controls the movement of cells in a tissue by regulating cell adhesion. This same mechanism may be defective in diseases such as cancer and its metastasis, when tumour cells lose their adhesion to neighbouring cells and migrate through the organism. The results of this research have been published in this week's Nature Cell Biology.

Specialists in development, Daniel Shaye, Jordi Casanova and Marta Llimargas, have studied the mechanisms that control cell movements during trachea development in the fly Drosophila. In this process, cells that initially form column of two cells deep, change their position to line up one after the other in a single file. A key element in the regulation of these movements is the amount of adhesive protein E-Cadherin located in the cellular membrane. Jordi Casanova, head of the Morphogenesis in Drosophila at IRB Barcelona, explains that "when movement starts, the levels of this protein in the cells decrease, thereby allowing them to slide one on top of the other, and once in this position the levels of this protein are re-established in order to seal the new binding alignment". The in-depth study of this phenomenon has led to the finding that the amount of E-Cadherin on the cell surface is controlled by the trafficking of this protein inside the cell and the identification of the elements that regulate this transport. During the experiments, the researchers induced or blocked cell movement by modifying the elements that control the trafficking of adhesive protein towards the membrane. "We demonstrate a mechanism that explains how cells can change their position within a given tissue. The sequence is clear: the greater the amount of protein, the greater the adhesion and the smaller the movement", recaps Casanova.

A mechanism may be dysfunctional during cancer progression and metastases

The role of E-Cadherin in the binding between epithelial cells is universal in all animals and therefore, following logic, the researchers believe that the mechanisms that regulate the levels of this protein may also be universal. "We speculate that the regulatory mechanism that we have discovered may also be present in other developmental contexts. However, in addition, fundamental elements of the mechanism may show a dysfunction in pathological processes such as the progression of cancer and metastases", adds Casanova. As revealed by this same researcher, the amounts of E-Cadherin and of one of the elements required for trafficking decrease in the progression of a kind of oesophagus cancer and this effect is related to the gain in tumour cell motility, which allows them to spread throughout the body more rapidly.

Thanks to this study, researchers working on cancer will be able to use animal models to test whether this mechanism is defective in other kinds of tumours and to study whether any of its genetic components are valid as therapeutic targets.

Institute for Research in Biomedicine (IRB Barcelona)

Cell Movements: From Molecules to Motility
by Dennis Bray (Author)

Cell Movements vividly describes how complex movements can arise from the properties and behaviors of biological molecules. This second edition is updated throughout with recent advances in the field and has a completely revised and redrawn artwork program. The text is suitable for advanced undergraduates as well as for professionals wishing for an overview of this field.

Cell Movement and Neoplasia. Ed by M. De Brabander. Proceedings of the Annual Meeting Held at Janssen Research Foundation, Beerse, Belgium, May 1979
by Cell Tissue and Organ Culture Study Group (Author)

Biomechanics of Active Movement and Deformation of Cells: Proceedings of Institute Held in Istanbul, Turkey, Sept. 1989 (Nato a S I Series Series H, Cell Biology)
by Turkey) NATO Advanced Study Institute on Biomechanics of Active Movement and Deformation of Cells (1989 : Istanbul (Author)

Cytomechanics is the application of the classical principles of mechanics in cell biology. It is an applied science concerned with the description and evaluation of mechanical properties of cells and their organelles as well as of the forces exerted by them. Thus, this topic needs a truly interdisciplinary approach, and accordingly this volume gives an up-to-date account of the current research done on cell division, mitosis, cytokinesis, cell locomotion and cell deformation during normal development and the cytoskeletal role in cell shape. Biologists, biomechanicians, biophysicists, biochemists and biomathematicians here discuss the basic concepts of mechanics and thermodynamics, emphasizing their applicability to cell activities.

Biomechanics Active Movement Cells (NATO Asi Series)
by Akkas (Author), Nuri Akkas (Editor)

The book is the result of interdisciplinary collaboration between scientists from the diverse fields of cell biology, biomechanics, biophysics, biochemistry, engineering, mathematics, and computational sciences. It provides detailed and appropriate mechanical explanations for the causes and consequences of active motion of cells, such as division, locomotion, shape change, and force generation. Also discussed is the applicability of the results in physiology, diagnosis and therapy.

Molecules and cell movement (Society of General Physiologists series ; v. 30)
by Raven Press (Publisher)

Mitosis: The movements of chromosomes in cell division (Columbia biological series)
by Franz Schrader (Author)

Cell Migration: Developmental Methods and Protocols (Methods in Molecular Biology)
by Claire M. Wells (Editor), Maddy Parsons (Editor)

Cell migration is a key component of many biological processes including embryonic development, immune responses, wound healing, organ regeneration, and cancer cell metastasis, thus making it an exciting and crucial field of study. The aim of Cell Migration: Developmental Methods and Protocols, Second Edition is to bring together a wide range of these techniques from the more basic migration assays, which are still the foundation of many cell migration studies, to state-of-the-art techniques and recent technical advances. Divided into three convenient parts, the volume begins with a number of basic in vitro migration assays including measurements of wound healing, cell scattering, invasion, and chemotaxis, as well as more complex measurements of transendothelial migration, the use of...

Cell Migration: Signalling and Mechanisms (Translational Research in Biomedicine)
by Frank Entschladen (Editor), Kurt S. Zanker (Editor)

Cell migration is a highly complex process which involves several compartments of the cell, including surface receptors, signalling elements and the cytoskeleton. It plays an essential role in embryogenesis, wound healing and inflammatory responses, and a dysregulation of cell movement can cause pathological states such as developmental defects, chronic inflammation, cancer invasion and metastasis. Covering extracellular regulatory signals and intracellular signal transduction pathways as well as the molecular mechanisms of migration in stem cells, leukocytes and tumor cells in the adult human organism, this book summarizes the current state of knowledge about cell migration. In the first part, the major aspects of different migratory cells in health and disease are covered, with special...

Cell Motility: From Molecules to Organisms (Life Sciences)
by Anne Ridley (Editor), Michelle Peckham (Editor), Peter Clark (Editor)

Recent advances in molecular and biophysical techniques, particularly fluorescence and live cell imaging, are revolutionizing the study of cell motility. New bioprobes not only reveal simple intracellular localization, but also contain details of post-translational modifications, conformational state and protein-protein interactions. Coupling these insights with complementary advances in genetic and biochemical methods is enabling scientists to understand the processes involved in cell motility - from molecular motors to cell movements in vivo in a range of organisms and cell types.

This book features landmark essays that provide an up to date and fascinating account of current research and concepts in cell motility.These cover the roles of molecular motors that drive movement and...

Cell Motility (Biological and Medical Physics, Biomedical Engineering)
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A much-needed work that provides an authoritative overview of the fundamental biological facts, theoretical models, and current experimental developments in this fascinating area. Cell motility is fundamentally important to a number of biological and pathological processes. The main challenge in the field of cell motility is to develop a complete physical description on how and why cells move. For this purpose new ways of modeling the properties of biological cells have to be found – and this volume is a major stepping-stone along the way.