Identifying novel regulators of colorectal cancer invasion

Details

Cancer metastasis accounts for around 90% of cancer deaths. While the survival rate has been improved over the years through early diagnosis, limited progress has been made in the targeting of metastasis. This stems from a fundamental lack of understanding of the basic biology underlying this process. While flies have emerged as powerful tool to investigate tumour growth and identify cancer related pathways, to-date studies have been limited by a lack of metastatic models where cells can be followed from primary tumour development to secondary tumour formation in adult organisms. We recently overcame this longstanding limitation, developing the first model for the induction of macrometastases in adult Drosophila melanogaster.

This project aims to now leverage this model to identify the cellular and molecular mechanisms that underlie the first steps of cell dissemination from the primary tumour. This will involve developing methods to live image tumour cell dissemination from primary tumours, and out of a complex organ, on our labs own dedicated multiphoton confocal. In parallel, genomics data existing within the lab will be mined to identify candidate genes. Combining live and fixed confocal analysis, as well as sensitive luciferase assays for each step of the metastatic process, these candidates will be investigated for a functional role in tumour metastasis. Overall, we expect the findings from the project to provide new insight into the complex process of cancer metastasis, as well as provide novel prognostic and therapeutic markers for metastatic colorectal cancer.

Funding Notes

Self-funding applicants only.

References

“Lab website

https://cellplasticity.weebly.com/publications.html

Recent publications from the lab

Plygawko, A.T., Adams, J., Richards, Z. and Campbell, K. (2025) A hormonally regulated gating mechanism controls EMT timing to ensure progenitor specification occurs prior to epithelial breakdown. BioRxiv. doi: 10.1101/2025.07.19.665116

Montes-Labrador, M., Campbell, K. and Casali, A. (2025) Drosophila as a model for metastasis. Advances in Experimental Medicine and Biology. doi: 10.1007/978-3-031-97035-1_8.

Jonckheere, S., Taminau, J., Adams, J., Haerinck, J., De Coninck, J., Verstappe, J., De Clercq, K., Peeters, E., Gheldof, A., De Smedt, E., Goossens, V., Audenaert, D., Candi, A., Versele, M., De Groote, D., Verschuere, H., Stemmler, M., Brabletz, T., Vandenabeele, P., Casali, A., Campbell, K., Goossens, S. and Berx, G. (2025). Development and validation of a high-throughput screening pipeline of compound libraries to target EMT. Cell Death and Differentiation. doi: 10.1038/s41418-025-01515-6.

Plygawko, A.T, Stephan-Otto Attolini, C., Pitsidianaki, I., Cook, D.P., Darby, A.C and Campbell, K. (2024) The Drosophila adult midgut progenitor cells arise from asymmetric divisions of neuroblast-like cells. Developmental Cell. doi: 10.1016/j.devcel.2024.10.011

Parisi, E., Hidalgo, I., Montal, R., Pallisé, O., Tarragona, J., Sorolla, A., Novell, A., Campbell, K., Sorolla, M.A., Casali, A. and Salud, A. (2023) PLA2G12A as a novel biomarker for colorectal cancer with prognostic relevance. International Journal of Molecular Sciences. doi: 10.3390/ijms241310889.

Sharpe, J.L., Morgan, J., Nisbet, N., Campbell, K. and Casali, A. (2023) Modelling cancer metastasis in Drosophila melanogaster. Cells. doi: 10.3390/cells12050677.

Jonckheere, S., Adams, J., De Groote, D., Campbell, K., Berx, G. and Goossens, S. Epithelial-Mesenchymal Transition (EMT) as a therapeutic target. (2022) Cells Tissues Organs. doi: 10.1159/000512218

Pitidianaki, I., Morgan, J., Adams, J. and Campbell, K. (2021) Mesenchymal-to-epithelial transitions require tissue-specific interactions with distinct laminins. Journal of Cell Biology. doi: 10.1083/jcb.202010154

Adams, J., Casali, A. and Campbell K. (2021) Sensitive high-throughput assays for tumour burden reveal the response of a Drosophila melanogaster model of colorectal cancer to standard chemotherapies. International Journal of Molecular Sciences. doi: 10.3390/ijms22105101”