Cancer is a devastating disease: more than one in three people in the UK will develop cancer in their lifetime. Metastasis is the primary cause of cancer related deaths. Crucially, any potential treatment of metastasis, which may target increased migration, needs to take into account that cancer cell migration is plastic, i.e. that cancer cells can easily switch between a Rac-Scar/WAVE-Arp2/3 actin polymerisation-driven mesenchymal and RhoA contractility driven amoeboid migration mode. The latter mode can be induced by confining cells. However, it is not known how cancer cells can actively switch between these two modes.
Rac-Scar/WAVE promotes mesenchymal migration and its inhibition increases RhoA-ROCK-MyosinII-dependent amoeboid migration. Amoeboid migration is favoured by some cancers including melanomas, while mesenchymal migration is utilised by some other cancers.
In this project, which will start in February or June 2026 you will investigate a novel mechanosensor that may act as a physiological switch between mesenchymal and amoeboid 3D cancer cell migration using biochemistry, molecular biology, and advanced live cell imaging.
We have unpublished data showing that a novel protein inhibits mesenchymal migration and also controls RhoA activity through a novel mechanism. We already mapped and mutated the respective binding sites. You will use CRISPR-Cas9 to genome edit cancer cell lines and/or use knockdown-rescue approaches to compare re-expression of wild-type or mutated cDNA in 3D video-microscopy assays and analyse the extent of amoeboid or mesenchymal migration. You will also produce microfluidic microchannels to investigate its role in controlling migration in confinement using above cell lines.
This novel regulator may also act as a mechanosensor since it translocates to the nucleus on stiffer matrices. It may function in the nucleus by changing the gene expression of cell migration regulators. You will further map nuclear import and export signals. You will perform RNAseq gene expression analysis comparing CRISPR knockout and re-expression of nuclear-export and -import mutants.
Taken together, your PhD work will unravel a novel and general mechanism of the control of switching between amoeboid and mesenchymal cell migration modes and how it contributes to cancer progression.
You will join a friendly, interactive, science driven lab, which is embedded in the Cytoskeleton and Cell Motility Section of the Randall Centre at King’s College London:
with 9 laboratories all interested in the cytoskeleton and cell motility with joint meetings and journal clubs. Furthermore, we are part of the London wide London Cell Motility Club, which I am organizing.