Biology subjects

Morretton, J.-P.

Publications and source records attributed to Morretton, J.-P..

3 recordsLinked to original sources

bioRxiv2025

Associative memory in human cancer cells

In psychology and neuroscience, associative memory refers to the capacity to learn and remember a link between two unrelated items. Although associative memory is widely believed to be restricted to animals possessing a complex nervous system, several reports have suggested that single-cell organisms can be conditioned to develop an associative memory-like behavior. Here, we report that human cancer cell lines can be conditioned to associate an extracellular matrix component and Gefitinib, a drug that reduces cell migration velocity. Collagen-I was periodically paired with Gefitinib and we observed that conditioned cells progressive decreased migration velocity on collagen-I but not on other extracellular matrix components. We identified the adenosine receptor ADORA2A as a key actor regulating the acquisition of associative memory. We also observed that the magnitude of the conditioned response oscillated over time with the same periodicity as paired stimuli presentations during conditioning. We found that mitochondria morphology oscillated with the same periodicity, suggesting that memory and energy metabolisms are linked. We propose that human cancer cells can be conditioned to integrate a link between two stimuli from their environment in a process that may allow to anticipate future stress exposition.

cell biology↗

bioRxiv2023

Centrosome amplification primes for apoptosis and favors the response to chemotherapy in ovarian cancer beyond multipolar divisions

Centrosome amplification is a feature of cancer cells associated with chromosome instability and invasiveness. Enhancing chromosome instability and subsequent cancer cell death via centrosome unclustering and multipolar divisions is an aimed-for therapeutic approach. Here we show that centrosome amplification favors responses to conventional chemotherapy independently of multipolar divisions and chromosome instability. We perform single-cell live imaging of chemotherapy responses in epithelial ovarian cancer cell lines and observe increased cell death when centrosome amplification is induced. By correlating cell fate with mitotic behaviors, we show that enhanced cell death occurs independently of chromosome instability. We identify that cells with centrosome amplification are primed for apoptosis. We show they are dependent on the apoptotic inhibitor BCL-XL, and that this is not a consequence of mitotic stresses associated with centrosome amplification. Given the multiple mechanisms that promote chemotherapy responses in cells with centrosome amplification, we assess such a relationship in an epithelial ovarian cancer patient cohort. We show that high centrosome numbers associate with improved chemotherapy responses and longer overall survival. Our work identifies apoptotic priming as a clinically relevant consequence of centrosome amplification, expanding our understanding of this pleiotropic cancer cell feature.

cell biology↗

bioRxiv2019

Centrosome amplification favours survival and impairs ovarian cancer progression

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers of human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of human epithelial ovarian cancers (EOCs) from 100 patients. Using state-of-the-art microscopy, we have determined the Centrosome-Nucleus Index (CNI) of each tumor. We found that EOCs show infrequent centrosome amplifications. Strikingly, the large majority of these tumors presented low CNIs. We show that low CNI tumors are enriched in the mesenchymal subgroup and correlate with poor patient survival. Our findings highlight a novel paradigm linking low centrosome number with highly aggressive behavior in ovarian cancers and show that the CNI signature may be used to stratify ovarian cancers.

cancer biology↗