Publication Highlights: Nov/Dec 2020

In a preprint available on bioRxiv (Absent expansion of pericentral hepatocytes and altered physiology in Axin2CreERT2 mice), postdoc Stephanie May and fellow researchers at the Beatson Institute reconcile discrepancies found in previous lineage tracing studies of hepatocytes. Using a CreERT2 construct knocked into the endogenous Axin2 locus, the team found no evidence of expansion of the labelled hepatocytes. They also report that this mutant allele results in profound perturbation of the Wnt pathway and physiology in the mouse.

CYRI-B inhibits actin assembly, by competing with Scar/WAVE for interaction with Rac1. In a new study (Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1), postdoc Tamas Yelland and PhD student Anh Hoang Le reveal the nature of this interaction, presenting the crystal structures of CYRI-B and the CYRI-B:Rac1 complex. They show that CYRI-B has two subdomains: an N-terminal Rac1 binding subdomain and a C-terminal Ratchet subdomain that undergoes conformational changes induced by Rac1 binding. In a related study now available on bioRxiv (CYRI-A regulates macropinocytic cup maturation and mediates integrin uptake, limiting invasive migration), Anh Hoang Le and others at the Beatson Institute also show that CYRI-A is recruited to nascent macropinosomes (cup-like structures at the cell surface that are important for nutrient uptake and regulation of cell surface receptor levels). They show that CYRI-A enables resolution of the macropinocytic cup by suppressing actin dynamics. Furthermore, the team also reveal that CYRI-A plays an important role in internalising integrins from the cell surface.

With current clinical practice, it is not possible to identify which prostate cancer patients are at high risk of early disease recurrence following androgen deprivation therapy (ADT). Addressing this issue, Gaurav Malviya, Rachana Patel and co-authors have used human prostate cancer orthograft models to study uptake of 18F-Fluciclovine following ADT (18F-Fluciclovine mirrors the uptake of glutamine, which plays a key role in cancer metabolism). In the study (18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy), the team find intra-tumoral heterogeneity in uptake that may explain treatment resistance. Such 18F-Fluciclovine imaging may help clinicians to identify patients at high risk of early cancer recurrence and therefore provide the opportunity to consider additional treatment.

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