05th July 2021
This month, we were delighted to see the translation of doctoral research into three outstanding scientific publications.
Valentin Barthet and Beatson colleagues progressed our understanding of the cell of origin in liver cancer. In a new preclinical model driven by the loss of a cellular recycling process called macroautophagy and the tumour-suppressor gene PTEN, mature liver cells developed into stem cell-like progenitors giving rise to cancerous cells. On a molecular level, the activation of YAP together with TAZ also highlighted possible new avenues for treatment intervention in liver cancer. [Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver in Science Advances]
Aldo Bader together with Martin Bushell introduced a new program in the latest edition of DNA Repair – through a curated database, this allows for quick and simple meta-analyses of published studies together with the users’ own data investigating DNA repair. In his own studies, Aldo identified a network of novel DNA repair genes linked to the progression of cancer of the adrenal gland. The software is free to download from: http://damage-net.co.uk/
Together with a team of Beatson scientists, Anh Hoang Le characterised the cellular role of the protein CYRI-A in his recent article in Journal of Cell Biology. Within cells, the researchers placed CYRI-A at the site of membrane extensions that facilitate the uptake of cargo from the extracellular space. Further work is required, but the authors suggested that CYRI-A takes a regulating role and forces, in particular, the engulfment of external cargo. Through this, CYRI-A together with its paralogue CYRI-B also impacted the cells’ ability to adhere and spread to distant sites, such as in cancer metastasis.
Cargo proteins help other proteins maintain their stability when travelling through the cell body. Tamas Yelland, Esther Garcia, Youhani Samarakoon, together with Shehab Ismail characterised the cargo protein UNC119B, solving its crystal structure. With a focus on biochemical differences to its paralogue UNC119A, UNC119B showed overlapping but not identical cargo binding, facilitated by a specific negatively charged site within its structure. [The Structural and Biochemical Characterization of UNC119B CargoBinding and Release Mechanisms in Biochemistry]
By comparing protein signatures across multiple cell models Beatson scientists Kelly Hodge, Sergio Lilla and Sara Zanivan, in a collaboration led by a team at MD Anderson Cancer Center, Texas revised the suite of classic exosome markers. Among 22 enriched core protein markers, they identified Syntenin-1 as the most abundant protein in exosomes. The information generated in this Nature Cell Biology article provides a comprehensive resource for the scientific community interested in the basic biology of exosomes and their translational application.
The Sansom lab continued to develop new insights into the biology underlying colorectal cancer. In their recent Nature article, scientist Dustin Flanagan together with collaborators identified the protein NOTUM as a key factor that allows APC-mutant cells to outcompete non-mutant cells in the intestinal crypt and therefore aid cancer formation. In a recent Nature Communications study, Josh Leach and fellow researchers developed a new preclinical model of right-sided bowel cancer that faithfully mimics human disease. Initial molecular observations of the involvement of YAP signalling and local inflammation set starting points for the development of new, effective therapies and early detection approaches for colorectal cancer.
