ArticleInternational journal of molecular sciences2018
Simulated Microgravity Reduces Focal Adhesions and Alters Cytoskeleton and Nuclear Positioning Leading to Enhanced Apoptosis via Suppressing FAK/RhoA-Mediated mTORC1/NF-κB and ERK1/2 Pathways.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Effects of theInternational journal of molecular sciences · 2021Pooled it
- The effect of microgravity and flows on the organization and dynamics of the human genome.Science advances · 2026Article
- Impact of Microgravity on Cytoskeletal Dynamics, Protein Transport, and Signaling Networks: Potential Therapeutic Opportunities for Skin Health.International journal of molecular sciences · 2026Review
- Skeletal muscle adaptation to microgravity: how altered mechanical cues drive catabolic signaling.EMBO reports · 2026Review
- A systematic review of microgravity on reproductive systems: Implications for space biology and human health.iScience · 2026Review
- Microgravity and cancer cells: from molecular mechanisms to therapeutic strategies.Cell death discovery · 2026Review
- Cell biomechanics on muscle atrophy: from intricate mechanisms to therapeutic frontiers.Annals of medicine · 2025Review
- Immune System-Tumor Crosstalk Under Microgravity: Mechanistic Insights, Challenges, and Translational Perspectives.Cancers · 2025Review
- Aging and Altered Gravity: A Cellular Perspective.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Focal Adhesion Kinase Alleviates Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation by Activating Transcriptional Wnt/β-Catenin-BMP2-COL1 and Metabolic SIRT1-PGC-1α-CPT1A Pathways.International journal of molecular sciences · 2025Article
- Simulating Space Conditions Evokes Different DNA Damage Responses in Immature and Mature Cells of the Human Hematopoietic System.International journal of molecular sciences · 2023Article
- YAP Inhibition Alleviates Simulated Microgravity-Induced Mesenchymal Stem Cell Senescence via Targeting Mitochondrial Dysfunction.Antioxidants (Basel, Switzerland) · 2023Article
- Review
- Activation of Focal Adhesion Kinase Restores Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation via Wnt/Β-Catenin Pathway.International journal of molecular sciences · 2022Article
- The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model.International journal of molecular sciences · 2022Review
- Cancer Studies under Space Conditions: Finding Answers Abroad.Biomedicines · 2021Review
- Biological and Mechanical Characterization of the Random Positioning Machine (RPM) for Microgravity Simulations.Life (Basel, Switzerland) · 2021Article
- The CellBox-2 Mission to the International Space Station: Thyroid Cancer Cells in Space.International journal of molecular sciences · 2021Article
- Gravitational Experimental Platform for Animal Models, a New Platform at ESA's Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models.International journal of molecular sciences · 2021Review
- LKB1 Regulates Goat Intramuscular Adipogenesis Through Focal Adhesion Pathway.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simulated-microgravity (SMG) promotes cell-apoptosis. We demonstrated that SMG inhibited cell proliferation/metastasis via FAK/RhoA-regulated mTORC1 pathway. Since mTORC1, NF-κB, and ERK1/2 signaling are important in cell apoptosis, we examined whether SMG-enhanced apoptosis is regulated via these signals controlled by FAK/RhoA in BL6-10 melanoma cells under clinostat-modelled SMG-condition. We show that SMG promotes cell-apoptosis, alters cytoskeleton, reduces focal adhesions (FAs), and suppresses FAK/RhoA signaling. SMG down-regulates expression of mTORC1-related Raptor, pS6K, pEIF4E, pNF-κB, and pNF-κB-regulated Bcl2, and induces relocalization of pNF-κB from the nucleus to the cytoplasm. In addition, SMG also inhibits expression of nuclear envelope proteins (NEPs) lamin-A, emerin, sun1, and nesprin-3, which control nuclear positioning, and suppresses nuclear positioning-regulated pERK1/2 signaling. Moreover, rapamycin, the mTORC1 inhibitor, also enhances apoptosis in cells under 1 g condition via suppressing the mTORC1/NF-κB pathway. Furthermore, the FAK/RhoA activator, toxin cytotoxic necrotizing factor-1 (CNF1), reduces cell apoptosis, restores the cytoskeleton, FAs, NEPs, and nuclear positioning, and converts all of the above SMG-induced changes in molecular signaling in cells under SMG. Therefore, our data demonstrate that SMG reduces FAs and alters the cytoskeleton and nuclear positioning, leading to enhanced cell apoptosis via suppressing the FAK/RhoA-regulated mTORC1/NF-κB and ERK1/2 pathways. The FAK/RhoA regulatory network may, thus, become a new target for the development of novel therapeutics for humans under spaceflight conditions with stressed physiological challenges, and for other human diseases.
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Registered trials
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