Trevor Dale (website)
To determine whether the cancer-inducing loss of Axin1 and Axin2 proteins in the liver is mediated by changes to cell polarity.
3D liver organoid cultures generated from mice with Cre-loxP flanked alleles of Axin1 and Axin2 will be used to study the effects of deleting both anti-oncogenes. Cell biological, biochemical and gene expression studies will be used to identify the mechanisms by which Axin loss leads to cellular transformation. A particular focus will be paid to alterations in mitotic spindle orientation since Axin and its binding partners APC, b-catenin and GSK3 have previously been shown to associate with components of the centrosomal complexes and deregulation of physiological spindle-orientation in stem cell vs. progenitor decisions has been suggested to be a key step in oncogenesis.
- Dr. Sandrine Etienne-Manneville (Institut Pasteur)
- Prof. Dr. Anna Akhmanova (Utrecht University)
- Prof. Yohanns Bellaïche (Institut Curie)
- Dr. Marianne Ellis (University of Bath)
- Feng GJ, Cotta W, Wei XQ, Poetz O, Evans R, Jardé T, et al. Conditional disruption of Axin1 leads to development of liver tumors in mice. Gastroenterology. 2012 Dec;143(6):1650–9.
- Jardé T, Evans RJ, McQuillan KL, Parry L, Feng GJ, Alvares B, et al. In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89β-catenin system. Oncogene. 2013 Feb 14;32(7):883–93.
- Dale T, Clarke PA, Esdar C, Waalboer D, Adeniji-Popoola O, Ortiz-Ruiz M-J, et al. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol. 2015 Oct 26;