M-Lysosomes · Identification of a novel function of lysosomes in mitosis for cancer therapy

Identification of a novel function of lysosomes in mitosis for cancer therapy

Focus on mitosis is a long-standing strategy in cancer research to prevent the uncontrolled proliferation of malignant cells. Cancer cells have the capacity to highjack cellular pathways and bypass surveillance processes to survive. A common feature of cancer cells is their ability to tolerate high rate of errors during mitosis, also known as chromosomal instability (CIN). CIN is triggered by chromosome missegregation and induces chromosomal imbalance which was shown to cause intratumoral heterogeneity and the development of drug resistance in cancer cells. To prevent CIN, mitosis has to be timely and tightly regulated. The principal actor implicated in the degradation of mitotic factors is the ubiquitin-proteasome system (UPS) that leads to a rapid and sequential elimination of regulatory proteins. Interestingly, the involvement of the other cellular degradative system, aka the lysosomes, in regulating mitotic progression remains a controversial topic. The action “Identification of a novel function of lysosomes in mitosis for cancer therapy — M-Lysosomes” aimed to investigate whether lysosome-dependent degradation plays an active role during mitotic progression to identify a new therapeutic window for cancer treatment. Cancer is a burden in almost every family and is the second leading cause of death worldwide based on the World Health Organization. The impact of cancer on society ranges from emotional, economical and physical distresses. Even though incredible scientific and medical advances have revolutionized cancer treatments in the last decades, cancer remains a large and complex group of diseases with limited therapies. By interconnecting two prominent fields in cancer research, autophagy/lysosomes and cell division, the findings emerging from this Marie Skłodowska-Curie Action (MSCA) offer promising outcomes for cancer treatment with direct impact on both the scientific community and the society. The objectives of this project have been to (1) investigate whether lysosomes are involved in mitotic progression and (2) analyze the repercussion of dysfunctional lysosomes on chromosomal instability. This original and innovative scientific project demonstrated a protective function of lysosomes specifically during mitosis to prevent CIN. Our findings revealed an additional layer of complexity in the regulation of mitosis and opened new opportunities to design combination treatment for cancer patients. In addition, this MSCA Individual Fellowship aimed to foster the development of my professional career as an independent researcher.

Data: CORDIS, © European Union