Periodic Reporting for period 1 - MECHANOCHECK (ATR-mediated mechanotransduction and connections with the actin cytoskeleton)
Reporting period: 2016-04-01 to 2018-03-31
Using multidisciplinary techniques and experimental approaches, including AFM, micropattern and innovated cell stretching and cell compression device, we quantitatively studied how ATR acts on cellular and nuclear plasticity. We found that ATR functions control cell plasticity, which sense mechanical stress. Basically, ATR-defective cells become twice softer than normal cells. At spatio-temporal level, the mechano-response occurs primarily through the actin cytoskeleton, which forms the cellular mechanical system linking the extracellular microenvironment to the nucleus. We investigated the connection between ATR and actin and we surprisingly found out that ATR directly controls nuclear plasticity, which in turn controls cell plasticity, rather than play a role in actin organization and dynamics. ATR defective cells have compromised nuclear morphology and organization; these cells are highly susceptive to mechanical stress, and have a lower survive rate during interstitial migration. These results suggest that ATR could play an active role in influencing the metastatic process, thus implying that ATR may possess a tumorigenic function.
This line of research contributes to open new directions in the ATR field and to link the control of cellular and nuclear plasticity with the capability of cells in interstitial migration. Thus it might lead to novel target for cancer metastasis and new cancer drug discovery.
The results and developed novel techniques have been disseminated in a various conferences, including public and scientific communication initiatives. They have been also shared with companies to see the potential of commercialization.