Periodic Reporting for period 1 - CentrosoTME (The role of extra centrosomes on the tumour microenvironment)
Reporting period: 2019-06-01 to 2021-05-31
Recent work has shown that extra centrosomes drive tumour growth in vivo, indicating that centrosome amplification is not a bystander of cancer, but promotes tumorigenesis. Consistent with a direct role in cancer, we previously demonstrated that centrosome amplification leads to chromosome instability and cell invasion. In addition to the cell autonomous effects of centrosome amplification, our lab has new and exciting findings showing that centrosome amplification alters secretion and could globally influence components of the tumour microenvironment (TME), such as fibroblasts and immune cells. As the TME is important for cancer cell survival and metastasis, understanding the biology behind TME changes could lead to the development of novel therapeutic strategies. Currently there is no published link between centrosome amplification and TME. Therefore, this project started an exciting and novel research avenue bridging the centrosome and the TME fields.
The objectives of this project were 1) to characterize the TME in tumours containing extra centrosomes, 2) to identify factors from the cells with extra centrosomes that induce TME changes, 3) to target cells with extra centrosomes to prevent TME changes.
I found that centrosome amplification can globally impact the TME in a murine breast cancer model. Secreted factors related to TME changes were found to be more secreted by cells with extra centrosomes. Finally, I developed a tool to assess whether ablating cells with extra centrosomes can reduce the affected TME changes.