Patients affected by recessive dystrophic epidermolysis bullosa often develop life-threatening, aggressive skin cancer (SCCRDEB) with limited treatment options. Jasbani Dayal, Gareth Inman and colleagues found that although the response to blocking endogenous TGFβ signalling was diverse in SCCDREB samples, the treatment predominantly stopped cancer cell proliferation (in British Journal of Dermatology). This offers potential therapeutic benefits to these patients but clinical trials will need to proceed with caution due to the tumour-proliferative effects seen in a small number of patients.
Shashi Singh, Rob Insall and co-authors showed that the Scar/WAVE complex - a key driver for the formation of finger-like protrusions at the front edge of a cell – is phosphorylated after its activation, thus is not required for its activity. However, upon sensing physical adhesion, cells with phosphorylated Scar/WAVE complex demonstrated altered dynamics and size of projections, changing the cell's migration speed ("Cell–substrate adhesion drives Scar/WAVE activation and phosphorylation by a Ste20-family kinase, which controls pseudopod lifetime"). Investigating how cells move is important for understanding how cells travel in a physiological context such as cancer spread.
Alba Roca, Stephen Tait and other Beatson scientists found that "Venetoclax causes metabolic reprogramming independent of BCL-2 inhibition". The BH3-mimetic drug Venetoclax diminished mitochondrial function and inhibited the TCA cycle, a key biochemical reaction to release stored energy, through a mechanism not involving BCL-2. Although the authors observed mitochondria with an unusual shape and upregulation of the cell's integrated stress response in the drug-treated cells, the metabolic effects of Venetoclax on cells needs to be investigated further.
Together with other Beatson scientists, Syed Feroj Ahmed and Lori Buetow showed that the E3 ubiquitin ligase DTX2 recruits proteins commonly involved in DNA damage repair via the domain on its C-terminal (DTC). While PAR-modified proteins interact with DTX2 at an ADP-ribose-binding pocket at DTC, the RING domain facilitates substrate ubiquitination. This study establishes another mechanism of cross-talk between protein modifications, as seen for other signalling pathways.
