Centrosome amplification: not as clear cut as once thought
A new study from Dr Susana Godinho’s lab has revealed surprising insights into how cancer cells adapt to ‘centrosome amplification’ – a mechanism that they have previously demonstrated to be essential in allowing certain tumours to become aggressive and metastatic.
The findings of the research, published in The Journal of Cell Biology, show that a cancer cells’ ability to adapt to ‘centrosome amplification’ is not innate, instead reliant on additional changes including loss of a key protein called E-cadherin.
Indeed in a panel of breast cancer cell lines, the team found that high levels of centrosome amplification correlated with loss of E-cadherin.
In the future, these associated changes may help indirectly identify patients whose tumours are fuelled by ‘centrosome amplification’ through the development of relevant biomarkers.
Current approaches to identify cancer cells with extra centrosomes in the lab require much time and expertise.
These newer, more efficient approaches will be vital in allowing researchers and clinicians to develop better ways of targeting cells with extra centrosomes – now a common characteristic found in a variety of human tumours.
Another piece of the puzzle
Centrosomes are essential for organising the cellular skeleton and ensuring the even separation of genetic material from two opposite ends of the cell during division.
While healthy cells only have 2 centrosomes, human cancer cells often contain an amplified number and therefore require an efficient way of managing these in order to grow and divide equally.
To do this, cancer cells ‘cluster’ extra centrosomes close together.
What allows these cancer cells to cluster their centrosomes so efficiently? The current study provides some of the answers.
Following centrosome amplification, the team found that unlike cancer cells, healthy cells originating from similar human tissue are unable to cluster centrosomes efficiently, only being able to do so upon loss of a key cell-cell adhesion molecule called E-cadherin.
This loss is believed to allow more efficient ‘clustering’ by physically helping cells to bring centrosomes closer together during cell division.
The group’s data demonstrates that unlike previous observations, efficient centrosome clustering requires additional adaptation mechanisms that are unique to cancer cells and not shared by healthy cells from a similar background.
Loss of E-cadherin may identify a subset of future patients whose centrosome amplified tumours may be susceptible to targeted therapies such as clustering inhibitors.