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• W2316848049 abstract "Although genes associated with metastasis have been identified, the core intracellular events of the process remain obscure. Recently, it has been shown that cytoskeletal reorganisations, indicated by changes in the tensional force generated by the actin-myosin interaction in the cell, are critical for the development of invasive phenotypes. These changes are mediated in part by the microenvironment through mechanotransduction (6,7). Moreover, reduced cytoskeletal stiffness and increased mutability can distinguish metastatic cells from non[[Unsupported Character - Codename s]]invasive cancer cells and from normal cells. This suggests that many cancer cells are distinguished by altered physical properties and that biomechanical measurements of isolated cells may have significant diagnostic and prognostic value (2-4, 8). Thus, we hypothesize that by using isogenic cancer cell lines of differing metastatic potential transfected with fluorescently labelled motility reporter constructs, we will be able to elucidate altered mechanotransduction signalling as an important component in tumour formation and progression, which can then be studied mechanistically. We have recently demonstrated novel cytoskeleton dependent mechanotransduction pathways in heart (5) and skeletal muscle (1) cells in which stretch-dependent signal transduction activates the local production of reactive oxygen species (ROS) to trigger Ca 2+ signaling events. These discoveries were made possible by combining new mechano-optical techniques. We intend to apply this approach to further investigate abnormal kinase-mediated sensing of mechanical cues that may result in the development of fundamental abnormalities in the cancer microvasculature. We present preliminary data from different cancer lines that suggest manipulating kinase-mediated tension, using different inhibitors (ROCK inhibitor Y27632, MAPK inhibitor U0126), alone or jointly with one another can reprogram the tumour cells so that they normalize their reorientation response to cyclic strain and their ability to form networks (9). Citation Format: Leiam Colbert, Christopher W. Ward, Kenan Onel. A new approach to study intracellular pathways of metastasis in living tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1652. doi:10.1158/1538-7445.AM2013-1652" @default.
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• W2316848049 date "2013-04-15" @default.
• W2316848049 modified "2023-10-14" @default.
• W2316848049 title "Abstract 1652: A new approach to study intracellular pathways of metastasis in living tumor cells." @default.
• W2316848049 doi "https://doi.org/10.1158/1538-7445.am2013-1652" @default.
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