Publication Highlights: September 2020

Luke Tweedy, Robert Insall and colleagues at the Beatson report in Science ("Seeing around corners: Cells solve mazes and respond at a distance using attractant breakdown") that cells navigate complex environments such as man-made labyrinths by following and leaving chemical 'breadcrumbs', allowing pursuing cells to instantly find the shortest path and to avoid dead ends. This study helps us to understand how the environment and signals produced by other cells cue the direction of cancer spread.

Rob Wiesheu, Seth Coffelt and co-authors have made a pre-print available on BioRxiv ("Ly6C defines a subset of memory-like CD27+γδ T cells with inducible cancer-killing function"), which identifies a new subset of γδ T cells in mice that are similar to mature γδ T cells in humans. Culturing these cells stimulates their cancer-killing activity and opens up interesting opportunities for anti-cancer immunotherapy.

Chatrin Chatrin, Mads Gabrielsen, Danny Huang and Glasgow scientists describe a mechanism where ubiquitin itself becomes a target for post-translational modification ("Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases"). When binding NAD+, Deltex family E3 ligases facilitate the addition of ADP-ribose to ubiquitin (ADPr-Ub). This reversible process makes ubiquitin unavailable to the ubiquitin cascade and its associated regulatory machinery. The physiological role of ADPr-Ub, however, remains to be determined.

Together with their co-authors, Rafael Martinez and Hing Leung have distributed a preprint on BioRxiv ("Schlafen family member 5 (SLFN5) regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer") that provides large-scale analyses of proteins underlying three distinct castration-resistant prostate cancer models (CRPC). Although they identify distinct proteomic landscapes, SLFN5 is found at high levels in all models and is connected to poor outcome in patients. Mechanistically, SLFN5 changes the availability of metabolic building blocks in cells affecting a growth pathway underlying cancer.

Anna Koessinger, Dominik Koessinger, Jim Norman, and Stephen Tait together with other Glasgow cancer researchers ("Quantitative in vivo bioluminescence imaging of orthotopic patient derived glioblastoma xenografts") showcase a new technique to monitor long-term tumour growth in patient-derived glioblastoma models. Through imaging the overexpression of near-infrared fluorescent protein they have developed a method that is rapid, accurate and has clear advantages over conventional approaches.

Jacqueline Tait-Mulder, Alexei Vazquez together with Beatson Proteomics scientists link formate – its metabolism is increased in some cancer types – to the production of pyrimidine through the mTORC1 facilitated phosphorylation of CAD ("The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis"). How these events are linked to the tumour's higher demand for formate will need to be determined in future work

David Bryant and colleagues have shared a pre-print on BioRxiv ("Spatial enrichment of phosphoinositide metabolism is a molecular switch to promote metastasis") where they identify the protein IQSEC1 as a molecular mechanism to communicate to cancer cells whether to grow at the tumour site or become invasive and spread around the body. IQSEC1 directs the production of cellular messengers (phosphoinositides) to areas of the cells where forward stretching, invasive projections are formed. With the potential to reduce cancer spread, the inhibition of IQSEC1 makes an interesting target for potential therapeutic intervention.


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