## 4 Discussion
This partial transition to the mesenchymal phenotype, could help understand why the effect of microgravity on TCam-2 seminoma cells is more similar to what was observed in cells of a mesenchymal origin. In this paper, we also investigated the possible mechanisms in which microgravity can modulate the adhesive attitude of TCam-2 seminoma cells. Notably, we already demonstrated that simulated microgravity induced a transient increase of ROS production [27 ], and that the antioxidant administration prevented the simulated microgravity-induced autophagy and microtubule disorientation. These results indicated that simulated microgravity-activated ROS are responsible, at least in part, for the microgravity-induced modifications of cell physiology. Notably, autophagy is a way, in which cells react to the changing microenvironment, trying torescue their homeostatic phenotype, and it is relevant that this rescue mechanism is activated by microgravity-induced ROS production. In addition, we also reported that, among ROS, there was a significant microgravity-induced increase of the superoxide anion, the main oxidant produced by mitochondria. This together with the observed metabolic alterations and mitochondrial morphology modifications [1] brought us to hypothesize that the mitochondria network, and thus mitochondrial metabolic responses, could be the intracellular targets of the altered extracellular forces. However, there are also other intracellular sources that produce ROS, as the NADPH-oxidase enzymes [1], whose activity cannot be excluded. Noteworthy, it is fair to highlight that, in the last decade, scientific literature has changed the landscape on the actual role of ROS in normal cell physiology. Even though the ROS increase is frequently related to the cell oxidative stress, and in turn to cell damage. Several authors demonstrated that these products of mitochondria metabolism are key elements for cell responses to microenvironmental cues. The double-faced effects of ROS have been highlighted even in cancer progression and therapy [23]. This observation leads to a completely novel view of mitochondria functions, the mitohormetic theory, which states that mitochondria are not only energetic organelles but also cell \"sensors\" which modulate cellular responses [13]. This Copernican revolution revealed that many physiological processes are ROS-dependent, and the change of metabolism is not only related to energy production. By this point of view, mild stressors (such as microgravity exposure), triggering ROS production, help cells overcome microenvironmental changes, promoting all the cellular activities necessary to rescue their homeostatic phenotype. To this regard, it has been reported by several authors in different cellular models, that ROS are involved in cell adhesion and cell migration [14]. In the present paper, we demonstrated that ROS are necessary for the modification of the cadherin/catenin distribution pattern induced by the microgravity exposure, indicating that the adhesive attitude can be modified by mechanical force modification through modulating metabolism. This stimulates the intriguing hypothesis, which deserves further investigations, that the loss of cadherins in malignant transformation is not a final decision of the cells but could be modulated by controlling metabolic processes. Conceptualization, G.R. and M.A.M. ; methodology, G.R., C.M., A.C., M.C., K.C.S. ; validation, G.R., C.M., A.C., F.F. and M.A.M. ; formal analysis, A.C. and C.M. ; investigation, A.C., C.M., G.R. and M.A.M. ; resources, G.R., M.A.M. and C.S. ; data curation, C.S. ; writing--original draft preparation, G.R. ; writing--review and editing, G.R. and M.A.M. ; visualization, G.R., C.M., A.C., K.C.S., F.F., C.S. and M.A.M. ; supervision, G.R. and M.A.M. ; project administration, G.R. and M.A.M. ; funding acquisition, G.R. and M.A.M. All authors have read and agreed to the published version of the manuscript.