title: Phenotypic switch induced by simulated microgravity on MDA-MB-231 breast cancer cells.
abstract: Microgravity exerts dramatic effects on cell morphology and functions, by disrupting cytoskeleton and adhesion structures, as well as by interfering with biochemical pathways and gene expression. Impairment of cells behavior has both practical and theoretical significance, given that investigations of mechanisms involved in microgravity-mediated effects may shed light on how biophysical constraints cooperate in shaping complex living systems. By exposing breast cancer MDA-MB-231 cells to simulated microgravity (~0.001 g), we observed the emergence of two morphological phenotypes, characterized by distinct membrane fractal values, surface area, and roundness. Moreover, the two phenotypes display different aggregation profiles and adherent behavior on the substrate. These morphological differences are mirrored by the concomitant dramatic functional changes in cell processes (proliferation and apoptosis) and signaling pathways (ERK, AKT, and Survivin). Furthermore, cytoskeleton undergoes a dramatic reorganization, eventually leading to a very different configuration between the two populations. These findings could be considered adaptive and reversible features, given that, by culturing microgravity-exposed cells into a normal gravity field, cells are enabled to recover their original phenotype. Overall these data outline the fundamental role gravity plays in shaping form and function in living systems.
authors.affiliation: Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Piazza Sassari 3, 00161 Rome, Italy ; Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Masiello
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cucina
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Proietti
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Systems Biology Group, Viale Regina Elena 324, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palombo
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Coluccia
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: D'Anselmi
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Dinicola
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pasqualato
authors.affiliation: Department of Surgery "PietroValdoni", "Sapienza" University of Rome, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Morini
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Systems Biology Group, Viale Regina Elena 324, Via A. Scarpa 14, 00161 Rome, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Bizzarri
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D010641:Phenotype; D018474:Weightlessness Simulation
chemical_list: D003598:Cytoskeletal Proteins