Cells rely on their crampons to avoid slipping

These results, published in the Communications Biology journal, shed new light on how cells adhere or migrate, which are mechanisms essential to the good functioning of our organs but also involved in the development of metastatic tumours.

To ensure our survival, each cell performs specific functions in coordination with their neighbours. In this dynamic system, the migration of cells and their adhesion at the right place are essential.

But how do cells manage to coordinate with each other? Scientists have long believed that cells communicate mainly through chemical signals, such as hormones. However, recent discoveries suggest that mechanical signals play a major role in cell coordination.

“The significance of mechanical signals is still not fully understood. They are likely to play a key role in the regulation of tissues and individual cells,” says Professor Vesa Hytönen from Tampere University.

“This is why we started to study the ability of cells to decipher and respond to their physical environment”, explains Bernhard Wehrle-Haller, Professor at the Department of Cell Physiology and Metabolism at UNIGE’s Faculty of Medicine.

“This information could especially help us to understand how cancer cells use these mechanisms to invade other organs and form metastases,” Wehrle-Haller adds.

From a mechanical cue to a biological signal

When a cell has to move, it “senses” its environment with the help of integrins, the proteins on its surface. When the cell detects a suitable location, a complex network of proteins, called focal adhesion, is then set up to form cellular crampons that anchor the cell to its environment.

“We wanted to shed light on how this anchoring mechanism is regulated,” explains Marta Ripamonti, researcher in the laboratory of Professor Bernhard Wehrle-Haller and first author of the study.

By studying paxillin, one of the many proteins that make up these crampons, researchers were able to unravel the mystery.

Latifeh Azizi, who is working towards PhD at Tampere University analysed the interactions of paxillin with biosensor technology. She discovered that paxillin interacts with a protein called talin.

“We knew that this protein played a role in the assembly of focal adhesions, but we didn’t expect it to be the key regulator”, says Wehrle-Haller.

Without functional paxillin, cells are unable to anchor even though their environment would be suitable. In addition, paxillin has the function of informing the cell that anchoring has taken place correctly, thus transforming a mechanical response into a biological signal that the cell can understand.

Can metastases be prevented by disrupting the crampons?

These in vitro experiments highlight the major role of paxillin in the migration and adhesion of healthy cells, but they could also be a starting point for a better understanding of cancer development.

“It is likely that cancer cells use paxillin to find a place that enhance their survival. Would it be possible to block this mechanism in tumour cells and prevent the formation of metastases? Yes, we think so.” Wehrle-Haller concludes.

Ripamonti, M., Liaudet, N., Azizi, L. Daniel Bouvard, Vesa P. Hytönen & Bernhard Wehrle-Haller: Structural and functional analysis of LIM domain-dependent recruitment of paxillin to αvβ3 integrin-positive focal adhesions. Commun Biol 4, 380 (2021).
https://doi.org/10.1038/s42003-021-01886-9

Inquiries:
Professori Vesa Hytönen, vesa.hytonen [at] tuni.fi
 

Photo: University of Geneva