Using a lineage tracing model, Stephanie May and colleagues established that pericentral hepatocytes played only a limited role in the regeneration of the liver. Their Axin2CreERT2 knock-in model reconciled previously conflicting reports on the involvement of this cell type and revealed methodological challenges of preclinical modelling. [Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration]
In their study, Beatson scientists, led by David Byrant, showed that Podocalyxin (PODXL), a transmembrane protein that is part of the cell’s outer coating, promoted invasive behaviour in prostate cancer cells. Delivery of PODXL to the cell surface, rather than expression per se, enabled it to bind to GAL3 and therefore relay effects to the cell’s anchoring system, resulting in increased metastatic spread in vivo – as such, intervening with the localisation of PODXL to the cell membrane may be an attractive therapeutic target for restricting metastasis. [Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function]
In another publication in the Journal of Cell Biology, the Bryant lab screened the ARFome – a group of ARF proteins involved in membrane trafficking – for their involvement in the regulation of cell shape and movement in prostate cancer. Using multi-day, live imaging of 3D cell culture in combination with machine learning approaches, they identified ARF3 as a key regulating switch between whether cells move collectively or invade by being guided by a leading cell.
Downstream of cancer-associated mutations such as KRAS and mTORC, eIF4A1 operates as part of the eIF4F translational initiation complex which forms the basis of oncogene-induced dysregulated translation. In Nucleic Acids Research,Beatson scientists led by Tobias Schmidt and Martin Bushell, recently showed that the activation of eIF4A1 is controlled through RNA-sequence-dependent recruitment and multimerisation of eIF4A1. This results in localised unwinding of repressive RNA structure and ultimately translation of eF4A1-dependent mRNAs in cells.
