How cells communicate when they migrate collectively
Recently, scientists from BIOC, in collaboration with Institut Curie and the Mechanobiology Institute in Singapore, revealed a novel mechanism of cell coordination during collective cell migration. This process is critical for development as well as for healing injuries in adults; it is also involved in pathological processes such as cancer cell dissemination.
During collective migration, layers of cells gradually polarize in the direction of migration. This asymmetric polarization is superimposed on the apical-basal polarity of epithelial cells, adding another level of complexity to this phenomenon. Cell movement, polarization, and integration within a monolayer are all controlled by branched actin networks, which are rapidly generated by the Arp2/3 complex once it is activated.
Using a bioinformatic screen, the authors identified several proteins associated with branched actin. They then performed a functional CRISPR screen, in which each of these proteins was knocked out and cell behavior was characterized using PIV (particle image velocimetry), a method commonly used in physics to analyze fluid movements. In this approach, a field of view is divided into multiple sub-images, and displacement at each time point is identified using a mathematical algorithm, thus generating velocity fields. Finally, migration parameters can be extracted from these velocity fields and analyzed quantitatively.
“Thanks to this physics-based approach, learned from the group of Pascal Silberzan at the Curie Institute, we were able to quantitatively analyze multiple aspects of multicellular behavior when our genes of interest were inactivated by CRISPR,” explains Artem Fokin, the lead author of the study, working in the group of Alexis Gautreau. “We found that depletion of one of these genes, PKN2, led to discoordination of cell movement, as if the cells were disconnected from each other.”
Indeed, PKN2 was found to associate with lateral cell junctions in the moving monolayer, and its depletion led to a loss of E-cadherin enrichment at cell junctions. In collaboration with Jie Yan from the Mechanobiology Institute in Singapore, the researchers ultimately demonstrated that PKN2-depleted cells lacked E-cadherin-mediated cell-to-cell adhesion.
On the other hand, depletion of the second hit, MOB4, produced the most unusual phenotype of collective cell behavior, which the authors termed the “streaming” phenotype”. The term captures two phenomena observed in these cells: a loss of directionality in follower cells and excessive cell movement, together creating characteristic “streamlines” in the vector fields obtained through PIV analysis.
MOB4 knockout causes cell streaming
The authors further demonstrated that MOB4 tended to localize at the fronts of follower cells, consistent with its proposed role in sensing or transmitting a directional cue. Through a series of experiments, they demonstrated that MOB4 controls collective cell migration through activation of the transcription factor YAP1 in follower cells.
Therefore the authors propose a new model of collective cell migration regulation, where the two proteins. PKN2 and MOB4, play a central role. These findings open new avenues for studying planar cell polarity in mammalian cells, as well as the signaling mechanisms and gene-expression programs underlying collective cell behavior. These questions will form a significant part of the future research program at BIOC.
Reference: Fokin, A. I., Lin, Y., Guschin, D. Y., Chen, H.-Y., James, J., Yan, J., Silberzan, P., & Gautreau, A. M. Identification of PKN2 and MOB4 as Coordinators of Collective Cell Migration. Advanced Science (2026). DOI: 10.1002/advs.202502907.