Dr Susana Godinho
Queen Mary University of London
Cancer cells often contain extra centrosomes. The centrosome is the main microtubule-organizing centre in animal cells, an essential component of the cytoskeleton. In normal cells, centrosome number is tightly regulated, however, cancer cells tend to have too many centrosomes, a characteristic associated with tumour aggressiveness. Yet little is known about the role of centrosome amplification in tumour progression.
We currently focus on breast cancer to investigate how centrosome amplification impacts tumourigenesis in a variety of model systems, including 2-D and 3-D cell culture, and mouse models. We also collaborate with clinical scientists to use primary human tissue samples from patients in order to validate our findings.
1. How cancer cells ‘adapt’ to centrosome amplification
In order to avoid cell death, cancer cells need to cluster extra centrosomes into two poles during mitosis, enabling quasi-normal bipolar cell division. This observation has generated an enormous interest as it provides the basis for using the presence of extra centrosomes as a target for cancer therapies. We are currently developing novel strategies to assess how different cell types cope with extra centrosomes, allowing them to survive. We expect to use this knowledge to develop novel therapeutic strategies that specifically target cancer cells.
2. Impact of centrosome amplification in cancer cell physiology
Unlike normal cells that are very intolerant to centrosome amplification, cancer cells frequently maintain extra centrosomes. This observation suggests that centrosome amplification is advantageous for the tumour. To address this question we use a variety of model systems to investigate how extra centrosomes affect cell physiology. Since our work suggests that centrosome amplification promotes invasive behaviour, we are currently investigating signalling pathways that are important in invasion/metastasis.
3. Developing mouse models to study the impact of centrosome amplification in tumour progression in vivo.
We are collaborating with experts in mouse genetics to develop new model systems to investigate the impact of extra centrosomes in tumour progression in vivo.