Evidence map›Paper›PMID 29491429›Full record

ArticleScientific reports2018

Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways.

Xin Tan, Aizhang Xu, Tuo Zhao, Qin Zhao, Jun Zhang, Cuihong Fan, Yulin Deng, Andrew Freywald, Harald Genth, Jim Xiang

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Effects of theInternational journal of molecular sciences · 2021
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
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  8. Aging and Altered Gravity: A Cellular Perspective.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  9. Article
  10. Review
  11. Application of Microgravity Experiments in Plastic Surgery: A Literature Review.Plastic and reconstructive surgery. Global open · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Xin TanAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China.
Aizhang XuCancer Research, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan, S7N 4H4, Canada.
Tuo ZhaoAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China.
Qin ZhaoAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China.
Jun ZhangAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China.
Cuihong FanAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China.
Yulin DengAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China.
Andrew FreywaldDepartment of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada.
Harald GenthHannover Medical School, D-30625, Hannover, Germany.
Jim XiangAerospace Institute of Medical Engineering and Biotechnology, School of Life Sciences, Beijing Institute of Technology, Beijing, 10081, China. jim.xiang@usask.ca.
Beijing Institute of Technology · CNUniversity of Saskatchewan · CAMedizinische Hochschule Hannover · DESaskatchewan Cancer Agency · CA

Funding

CIHR OCH126276
6 · The paper itself

Abstract

Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases. We demonstrate that SMG inhibits NADH induction and glycolysis, but induces mitochondrial biogenesis. Interestingly, administration of a RhoA activator, the cytotoxic necrotizing factor-1 (CNF1) effectively converts SMG-triggered alterations and effects on mitochondria biogenesis or glycolysis. CNF1 also converts the SMG-altered cell proliferation and tumor metastasis. In contrast, mTORC inhibitor, rapamycin, produces opposite responses and mimics SMG-induced effects in cells at normal gravity. Taken together, our observations indicate that SMG inhibits focal adhesions, leading to inhibition of signaling FAK and RhoA, and the mTORC1 pathway, which results in activation of the AMPK pathway and reduced melanoma cell proliferation and metastasis. Overall, our findings shed a new light on effects of microgravity on cell biology and human health.

Indexed as

Focal AdhesionsSignal TransductionWeightlessness SimulationAMP-Activated Protein KinasesAnimalsCell Line, TumorCell ProliferationCytoskeletonEnzyme ActivationFocal Adhesion Kinase 1GlycolysisMechanistic Target of Rapamycin Complex 1MelanomaMiceMitochondriaNADAMP-Activated Protein KinasesFocal Adhesion Kinase 1Mechanistic Target of Rapamycin Complex 1NADPtk2 protein, mouserhoA GTP-Binding Protein

Identifiers

PMID29491429
PMCPMC5830577
OpenAlexW2806013815

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.