Jakub Gemperle

Former Marie Skłodowska-Curie Research Fellow in Wellcome Trust Centre for Cell-Matrix Research (WTCCMR), Division of Cell Matrix Biology & Regenerative Medicine, University of Manchester, UK, Caswell lab

Currently postdoctoral research associate at Institute of Molecular Genetics (IMG) of the Czech Academy of Sciences in Laboratory of Integrative Biology, Dr. Martin Gregor

​In this Endopos project, my main focus was/is on the migration and invasion of ovarian cancer cells in a 3D matrix and the functions of vesicle trafficking pathways, in particular the endocytic system (Rab11 family GTPases), in controlling cell-matrix interactions in cancer.

To study this, we have adopted an innovative method called magnetogenetics. This allowed us to manipulate the positioning of Rab25 endosomes within live cells with high precision. Our study shows that the localization of Rab25 vesicles to the plasma membrane is crucial for forming protrusions driven by actin, facilitating the invasive behavior of cancer cells. Our results demonstrate that Rab25 directs the delivery of formin FMNL1 and integrins, along with RhoA activation, to provide the signal to activate FMNL1-mediated actin polymerisation. This enables coordination of adhesion and protrusion formation with cytoskeletal dynamics, thereby promoting cell migration in 3D-matrix.

This finding challenges the previous hypothesis that endosomes primarily facilitate cargo placement to support protrusion formation/ cell migration. Instead, we provide evidence of their direct role in protrusion initiation. 

Our approach opens new avenues for future research in endosomal trafficking and the cytoskeletal field, enabling the exploration of causal relationships previously inaccessible with conventional methods.