Long-Term Simulation of Microgravity Induces Changes in Gene Expression in Breast Cancer Cells

Sahana, Jayashree; Cortés-Sánchez, José Luis; Sandt, Viviann; Melnik, Daniela; Corydon, Thomas J.; Schulz, Herbert; Cai, Zexi; Evert, Katja; Grimm, Daniela; Wehland, Markus

doi:10.3390/ijms24021181

Cited by 9 publications

(13 citation statements)

References 80 publications

(128 reference statements)

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“… PFC, 31 parabolas [ 189 ] MDA-MB-231 DEGs in MCS: AKT , KI67 , BCL2 , BAX , CD44 , and MMP9 after 72h; AKT , KI67 , BCL2 , and MMP9 after 24 h DEGs in RPM-AD: BAX , CD44 , and MMP9 after 72 h; BCL2 and MMP9 after 24 h RPM 24 h, 72 h [ 190 ] MCF-7, MDA-MB-231 qPCR-verified genes search in the mammalian phenotype database and the human genome-wide association studies (GWAS) Catalogue ERK1 , AKT1 , MAPK14 , EGFR , CTNNA1 , CTNNB1 , ITGB1 , COL4A5 , ACTB , and TUBB gene expression of MCSs differentially regulated in both cell types. 7 genes (ACTB, CD44, EGFR, ITGB1, PXN, TUBB, and VCL) were successfully analyzed using WCGNA RPM 14 d [ 191 ] Prostate cancer PC-3 3 d: Downregulation of VEGF , SRC1 , AKT , MTOR , and COL1A1 in MCS. No change in FLT1 , RAF1 , MEK1 , ERK1 , FAK1 , RICTOR , ACTB , TUBB , and TLN1 mRNAs.…”

Section: Resultsmentioning

confidence: 99%

“…A recent long-term s-µg study demonstrated an association between the real metastatic microtumor environment and breast cancer cells (MCF-7, MDA-MB-231) exposed to the RPM with respect to biological factors related to the extracellular matrix, cytoskeleton, morphology and different cellular signaling pathways [ 191 ]. It was shown that the key elements ( ERK1 , AKT1 , MAPK14 , EGFR , CTNNA1 , CTNNB1 , ITGB1 , COL4A5 , ACTB and TUBB ) were differentially expressed.…”

Section: Resultsmentioning

confidence: 99%

“…The WGCNA revealed 7 ( ACTB , CD44 , EGFR , ITGB1 , PXN , TUBB, and VCL ) out of 18 genes. The following enrichment analysis determined that this group of genes comprised the cluster of genes responding to the morphology of breast cancer ( Table 9 ) [ 191 ].…”

Section: Resultsmentioning

confidence: 99%

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Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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“…They include ocularvestibular changes, blood clotting and wound healing dysfunction, increased cellular turnover and the more widely appreciated cardiovascular and musculo-skeletal changes [45][46][47]. There is good evidence to support gene dysregulation, immune dysfunction and disturbances in cellular and immune signaling as the contributors to some of these effects [48]. These effects may or may not be coupled with increased radiation exposure, from which the Earth's gravitational field currently provides humans with protection [49,50].…”

Section: The Physiological Effects Of Altered Gravity Environmentsmentioning

confidence: 99%

2024

Int J Geriatr Gerontol

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The world community continues to move towards exploring the solar system, with exploration of our immediate solar system aimed at establishing intra-planetary colonies, first perhaps on our nearest Earth neighbour Mars. Long haul and intergenerational space flight, with intra-and perhaps extra-planetary colonisation, at the current level of technology, will probably create the need for geriatric space travel.Humans are uniquely adapted to a live, survive and thrive in Earth gravity (1g) of approximately 9.8m 2 . When humans move beyond this gravity and the Earth's protective gravitational field, human growth, development and physiology is impacted. This brings to the forefront two main areas of consideration: multi-morbidity and increasingly complex care needs of an active geriatric crew, whose skills, academia and practical knowledge may be required for longer, and more enduring working lives, and the physiological hostility of altered gravity environments.Whilst aging on Earth is a complex topic; altered gravity environments will bring even greater challenges. Bodily systems known to be affected by altered gravity environments include the immune, cardio-vascular and muscular-skeletal systems. Gross affects on these systems have been catalogued over the years; the most notable being rapid onset of osteopenia and osteoporosis, even after relatively short exposure to altered gravity environments of two weeks. Newer areas of study of the effects of altered gravity have broadened to include infection susceptibility and disruptions to the gastrointestinal-pulmonary and gastrointestinalskin axes. Nutritional changes caused by gastrointestinal microbiome imbalances can affect both the uptake of nutrients as well as medications, with possible impacts on cellular operations and perhaps cognition.In the altered gravity environment those individuals genetically predisposed to certain diseases may be at risk of accelerated onset of cognitive decline, immunological and physiological changes. This paper explores some of the known physiological stresses caused by altered gravity environments, highlighting the possibly of disease and aging insults that may be experienced by the geriatric astronaut.

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“…These changes occurred time-dependently and were dependent on the tumor type. In general, µg had impact on among others survival [195], apoptosis, adhesion, focal adhesion, migration, growth, the cytoskeleton, extracellular matrix, growth factors, several signaling pathways such as PAM, MAPK, and VEGF signaling [196][197][198].…”

Section: Breast Cancermentioning

confidence: 99%

Omics Studies of Tumor Cells under Microgravity Conditions

Graf,

Schulz,

Wehland

et al. 2024

IJMS

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Cancer is defined as a group of diseases characterized by abnormal cell growth, expansion, and progression with metastasis. Various signaling pathways are involved in its development. Malignant tumors exhibit a high morbidity and mortality. Cancer research increased our knowledge about some of the underlying mechanisms, but to this day, our understanding of this disease is unclear. High throughput omics technology and bioinformatics were successful in detecting some of the unknown cancer mechanisms. However, novel groundbreaking research and ideas are necessary. A stay in orbit causes biochemical and molecular biological changes in human cancer cells which are first, and above all, due to microgravity (µg). The µg-environment provides conditions that are not reachable on Earth, which allow researchers to focus on signaling pathways controlling cell growth and metastasis. Cancer research in space already demonstrated how cancer cell-exposure to µg influenced several biological processes being involved in cancer. This novel approach has the potential to fight cancer and to develop future cancer strategies. Space research has been shown to impact biological processes in cancer cells like proliferation, apoptosis, cell survival, adhesion, migration, the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors, among others. This concise review focuses on publications related to genetic, transcriptional, epigenetic, proteomic, and metabolomic studies on tumor cells exposed to real space conditions or to simulated µg using simulation devices. We discuss all omics studies investigating different tumor cell types from the brain and hematological system, sarcomas, as well as thyroid, prostate, breast, gynecologic, gastrointestinal, and lung cancers, in order to gain new and innovative ideas for understanding the basic biology of cancer.

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Long-Term Simulation of Microgravity Induces Changes in Gene Expression in Breast Cancer Cells

Cited by 9 publications

References 80 publications

Current Knowledge about the Impact of Microgravity on Gene Regulation

Current Knowledge about the Impact of Microgravity on Gene Regulation

Geriatric Space Travel©

Omics Studies of Tumor Cells under Microgravity Conditions

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