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Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be paradoxically protected from programmed cell death during weightlessness. These controversial results can be explained by considering the notion that the behavior of adherent cells dramatically diverges in respect to that of detached cells, organized into organoids-like, floating structures. We investigated both normal (MCF10A) and cancerous (MCF-7) breast cells and found that appreciable apoptosis occurs only after 72 h in MCF-7 cells growing in organoid-like structures, in which major modifications of cytoskeleton components were observed. Indeed, preserving cell attachment to the substrate allows cells to upregulate distinct Akt- and ERK-dependent pathways in MCF-7 and MCF-10A cells, respectively. These findings show that survival strategies may differ between cell types but cannot provide sufficient protection against weightlessness-induced apoptosis alone if adhesion to the substrate is perturbed.

Survival Pathways Are Differently Affected by Microgravity in Normal and Cancerous Breast Cells