News

Cadherin mechanotransduction in leader-follower cell specification during collective migration

A review article by Antoine A. Khalil and Johan de Rooij from UMC Utrecht have appeared in the Experimental Cell Research section of Elsevier

Collective invasion drives the spread of multicellular cancer groups, into the normal tissue surrounding several epithelial tumors. Collective invasion recapitulates various aspects of the multicellular organization and collective migration that take place during normal development and repair. Collective migration starts with the specification of leader cells in which a polarized, migratory phenotype is established.

Leader cells initiate and organize the migration of follower cells, to allow the group of cells to move as a cohesive and polarized unit. Leader-follower specification is essential for coordinated and directional collective movement. Forces exerted by cohesive cells represent key signals that dictate multicellular coordination and directionality. Physical forces originate from the contraction of the actomyosin cytoskeleton, which is linked between cells via cadherin-based cell-cell junctions.

The cadherin complex senses and transduces fluctuations in forces into biochemical signals that regulate processes like cell proliferation, motility and polarity. With cadherin junctions being maintained in most collective movements the cadherin complex is ideally positioned to integrate mechanical information into the organization of collective cell migration. Here we discuss the potential roles of cadherin mechanotransduction in the diverse aspects of leader versus follower cell specification during collective migration and neoplastic invasion.


Khalil, A.A., Experimental Cell Research, https://doi.org/10.1016/j.yexcr.2019.01.006

Iproteos, IBEC and VHIR to develop an innovative therapy against solid tumors

The biotechnology company Iproteos, IBEC and the Vall d’Hebron Research Institute (VHIR) are set to develop an innovative treatment to slow down, stop and even reverse the growth of solid tumors, which represent more than 90% of cancer cases.

It’s a family of peptidomimetic drugs based on a totally new anti-tumor action mechanism, the result of several years of research by Pere Roca-Cusachs’ group at IBEC.

The Translational Research Group on Cancer in Children and Teenagers at VHIR will evaluate candidate drugs, developed with Iproteos’ IPROTech technology, in pediatric tumours in vitro and in vivo.

Read more on the IBEC website.

Is the bottom-up approach enough to understand a whole system?

An opinion piece by IBEC group leader Xavier Trepat has appeared in the News and Views section of the current issue of Nature, which is devoted to ‘Bottom-up biology’.

In his piece ‘Bottom does not explain top’, Xavier argues that understanding how complex biological structures – or even entire cells – are built can only provide a certain amount of insight into how biological systems function at higher levels of organization. There are many variables such as density, or even pathologies suffered by the subject, that affect cell behavior at the mesoscale – that is, at the longer, more ‘system-level’ scale than that of the individual components of an organism. Cells in a group, for example, can sense or respond to external stimuli that an individual cell cannot identify.

Read more on the IBEC website

Third consortium meeting taking place at UMC Utrecht

Third consortium meeting taking place at UMC Utrecht

Mechano·Control is holding its third consortium meeting today at University Medical Center Utrecht.

Representatives from all seven partners – the UPC and Mind the Byte S.L. in Spain, UMC Utrecht and Noviocell B.V in the Netherlands, Germany’s Leibniz-Institut, and King’s College London – have gathered in the Netherlands for the meeting, which will present and discuss the state of the work packages and results so far.

During the meeting, issues related to the dissemination and exploitation of the project will also be reviewed.

Scientists discover super-stretchy cells

Scientists discover super-stretchy cells

Super-stretched cells surrounded by only slightly deformed ones. The cell nucleus is shown in blue, actin filaments in red, and keratin filaments in green.

One of the most enviable features of superheroes is their ability to stretch their bodies beyond imaginable limits. In a study published in Nature, scientists have discovered that our cells can do just that.

With every beat of the heart and every breath into the lungs, cells in our body are routinely subjected to extreme stretching. This stretching is even more pronounced when cells shape our organs at the embryo stage, and when they invade tissues through narrow pores during cancer metastasis – but how cells undergo such large deformations without breaking has remained a mystery until now.

This week, researchers at IBEC and the UPC report a new physical property of cells – which they’re calling active superelasticity – that may explain the unusual ability of cells to undergo extreme deformations.

The team, led by Marino Arroyo and Xavier Trepat (centre and right), developed a new approach to subject epithelial tissues – the thin cellular layers that cover internal and external surfaces of the body – to very large deformations, up to four times their original size. These cellular layers are fundamental to life, as they protect the body from radiation, pollutants and pathogens. They’re also responsible for gas exchange in the lungs, absorption of nutrients in the gut, and excretion of urine in the kidneys.

Read more on the IBEC website.

“In search of a new cure for cancer”

Is there chemo- and surgery-free cancer treatment in our future? Mechano·Control team of researchers are working to answer this question with a candidate solution against breast cancer. 

Latest CORDIS news and events post highlights Mechano·Control objectives and its connection to the TALVIN project, focused on the seek for a pancreatic cancer drug.

CORDIS (Community Research and Development Information Service) is the European Commission’s primary public repository and portal to disseminate information on all EU-funded research projects and their results in the broadest sense.

Read more on the CORDIS website.

Teaming up to unravel mechanosensing

Teaming up to unravel mechanosensing

These last weeks the group of Aránzazu del Campo at the Institute for New Materials (INM) in Saarbrücken has been host to another Mechano·Control member: Laura Faure, a postdoc from Pere Roca-Cusachs group at IBEC. Aleeza Farrukh, a Research Scientist at Dynamic Biomaterials group, has shared with Laura some advanced patterning techniques that she will implement in her assays. By combining single-cell traction force measurements and advanced patterning, researchers will try to decipher the role of cell-cell and cell-matrix forces during tumour growth and spreading.

In order to unravel the relationship between stiffness and tumour spreading, researchers need to look first at how cancer cells interact with their surrounding cells and tissue. With this idea in mind, IBEC and INM Mechano·Control members have joined efforts to merge their expertise into an advanced assay combining single-cell Traction Force Microscopy and 3D gel-patterning. “If we succeed, we will be able to quantify the impact of tissue stiffness on cell-cell and cell-matrix adhesions at the single-cell level”, Laura says. “To date, we don’t really know which forces trigger tumour spreading”, Aleeza adds. “This assay will help us understand the impact of rigidity changes in tumour growth and spreading in much more detail”. This is the third time that IBEC and INM teams meet to share skills and ideas within the project’s framework.

As part of Mechano·Control consortium strategy, partners have been sharing their know-how at all stages and scales of the project. Utrecht Research team has received several visits: from J Zanetta Zoi Kechagia, who spent 2 weeks working with organoids at their lab, to the visit of Noviocell sharing some samples with UMCU team. Also Johan De Rooij (UMCU) has been visiting del Campo (INM) in Saarbrücken and Mind the Byte has been working on its first drug candidate in tight interplay with De Rooij (UMCU) and Xavier Trepat (IBEC). Furthermore, Sergi Garcia-Manyes, head of Biological Physics & Soft Matter Group at King’s College London, has incorporated Amy Beedle, a postdoc holding a trans fellowship to visit several of the partners’ labs during her stay.

The next consortium meeting is to be celebrated in November the 16th, when all Mechano·Control partners will meet at Utrecht to discuss the project advances and the near future guidelines.

 

 

 

First IBEC PhD retreat a great success

First IBEC PhD retreat a great success

Last week IBEC’s PhD students headed off to Mas Colltort in Sant Feliu de Pallarols for the first ever IBEC PhD retreat. The two-day sojourn in the country was a chance for more than 50 of IBEC’s students to hear talks by various speakers, give flash presentations about their career paths, and get to know one another.

The invited speakers were Alfons Nonell‐Canals, CEO of Mind the Byte, who talked about ‘The thrill of being a scientific entrepeneur’; Dr. Vincenzo di Donato, Project Manager at ZeClinics, with ‘Jumping out from your comfort zone: straight from your PhD to Industry’; Pere Roca‐Cusachs, group leader at IBEC, with ‘How to progress in academia’; and IBEC postdoc Agata Nyga, who talked about ‘Surviving in research as an early career researcher: international perspectives’. There was also a workshop on ‘Molecules in the cloud: personalized medicine for everyone’ led by Mind the Byte.

 

Read more on the IBEC website

 

The way tumor cells expand challenges current physics

The way tumor cells expand challenges current physics

The photo features Xavier Trepat and Carlos Pérez, from IBEC, as well as Jaume Casademun, from UB.

Researchers from IBEC and UB have discovered that the way tumor cells expand defies the laws of physics.

In an article published today in Nature Physics, the researchers have challenged our current understanding of the discipline and developed a new framework that could help predict the conditions under which tumors initiate metastasis.

This discovery highlights the importance of physical forces in metastasis, opening the door to developing therapies to alter the mechanics of tumors as a possible treatment.

The study was financed by MINECO, the Generalitat de Catalunya, the European Research Council (ERC), the EC (under the MECHANOCONTROL project), CIBER-BBN and the Obra Social “La Caixa”.

Read more on the IBEC website

“A new type of cure for cancer on the horizon”

“A new type of cure for cancer on the horizon”

MECHANO-CONTROL Coordinator Pere Roca-Cusachs has been interviewed about the project for the CORDIS Digital Single Market news section.

Through the interview by Barbora Negolicka, Pere unfolds the project into its staples, to approach its strategy to decipher and treat breast cancer.

CORDIS (Community Research and Development Information Service) is the European Commission’s primary public repository and portal to disseminate information on all EU-funded research projects and their results in the broadest sense.

Read more on the CORDIS website