Our research group focuses on understanding how centrosome amplification impacts tumour progression and how we can target cells with amplified centrosomes to develop new cancer therapies.
Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion. Developmental Cell (2018) 47(4): 409-424. PMID: 30458137
Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells. Journal of Cell Biology (2018) 217(1):195-209. PMID: 29133484
Studying centrosome function using three-dimensional cell cultures. Methods in Cell Biology (2015) 129:37-50. PMID: 26175432
Oncogene-like induction of cellular invasion from centrosome amplification (2014). Nature (2014) 510(7503):167-71. PMID: 24739973
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 and pancreatic cancers to investigate how centrosome amplification impacts tumorigenesis 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.
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.
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.
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. We are particularly interested in understanding how cells with extra centrosomes communicate and influence the surrounding cells.
The principles of spindle bipolarity. Godinho SA Nat Rev Mol Cell Biol (2019) 20(2) 325
Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion. Arnandis T, Monteiro P, Adams SD et al. Dev Cell (2018) 47(2) 409-424.e9
Structural Centrosomal Abnormalities Push Cells toward Invasion. Monteiro P, Godinho SA Dev Cell (2018) 45(2) 286-288
Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation. Marteil G, Guerrero A, Vieira AF et al. Nat Commun (2018) 9(2) 1258
Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells. Rhys AD, Monteiro P, Smith C et al. J Cell Biol (2017) 217(1) 195-209
Dividing with Extra Centrosomes: A Double Edged Sword for Cancer Cells. Rhys AD, Godinho SA Adv Exp Med Biol 1002(1) 47-67
Centrosomes: PIDDosome Joins the Counting Game. Godinho S Curr Biol (2017) 27(2) R237-R239
DDR1 localisation to adherens junctions prevents efficient clustering of supernumerary centrosomes. Rhys AD, Vaghela M, Monteiro P et al. MOLECULAR BIOLOGY OF THE CELL (2016) 27(11)
Paracrine-mediated invasion induced by centrosome amplification. Arnandis T, Rajeeve V, Brennan CH et al. MOLECULAR BIOLOGY OF THE CELL (2016) 27(11)
Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes. Gibbons JG, Branco AT, Godinho SA et al. Proc Natl Acad Sci U S A (2015) 112(2) 2485-2490