centrosome abnormalities in cancer

Centrosomes are one of the main microtubule organising centres in animal cells and play important roles in the organisation and function of the microtubule cytoskeleton. Unlike most normal cells, that have conserved mechanisms to ensure that the correct centrosome number and structure are maintained, cancer cells, display various centrosomal abnormalities, such as centrosome amplification, that can promote chromosome instability and cell invasion. We want to understand how cancer cells carrying centrosome abnormalities are maintained in tumours and their impact to tumorigenesis. Because centrosome amplification can alter the secretion of proteins and extracellular vesicles, we are particularly interested in dissecting what drives this altered secretion and how it impacts cell-cell communication, tumour progression and evolution.

targeting cells with amplified centrosomes

Developing effective cancer therapies relies on identifying unique features of cancer cells that can be targeted. Unlike normal cells whose centrosome number is highly regulated, proliferating cancer cells can harbour amplified centrosomes. To avoid catastrophic multipolar divisions, cancer cells with amplified centrosomes can form pseudo-bipolar spindles by clustering extra centrosomes into two poles. Thus, preventing centrosome clustering can be used to preferentially kill cancer cells. Our goal is to understand what drives efficient clustering in cancer cells to identify effective ways to target cancer cells with amplified centrosomes.

Microtubules in stress and repair

Microtubules are polarised polymers that occupy most of the cytoplasm and can function as tracks for motors, such as kinesins and dynein, important for intracellular trafficking, polarity, cell division and migration. Microtubules can undergo posttranslational modifications – PTMs (e.g. acetylation, detyrosination) – that have been implicated in the regulation of their structure, dynamics and motor binding/activity, but its function is remarkably poorly understood. Interestingly, microtubule PTMs can respond to various stresses, such as DNA damage, oxidative stress and centrosome amplification. Our aim is to dissect how microtubules respond to stress and how this impacts intracellular repair mechanisms.

Image credit: Maria Fankhaenel

Image credit: Rob Dryden

Image credit: Lisa Donker