Evidence map›Paper›PMID 30577808›Full record

ArticleJournal of experimental & clinical cancer research : CR2018

SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4.

Ziming Li, Jia Huang, Shengping Shen, Zhenping Ding, Qingquan Luo, Zhiwei Chen, Shun Lu

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 36 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 3 pooled it
2.6field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Review
  6. Translational lung cancer research · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022
    Review
  14. Article
  15. Review
  16. Article
  17. Sirtuins and Hypoxia in EMT Control.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Ziming LiShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Jia HuangShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Shengping ShenShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Zhenping DingShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Qingquan LuoShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. luoqingquan@hotmail.com.
Zhiwei ChenShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. czw75@shchest.org.
Shun LuShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Jiao Tong University · CNShanghai Chest Hospital · CN

Funding

Clinical Research Plan of SHDC 16CR3005AFoundation for Shanghai Talent 201455Medical-Engineering Joint Funds from Shanghai Jiao Tong University YG2017MS81National Natural Science Foundation of China 81401880Shanghai Association for Science and Technology 16PJD043
6 · The paper itself

Abstract

backgroundEpithelial-to-mesenchymal transition (EMT) contributes to the invasion and metastasis of epithelial tumors. Sirtuin 6 (SIRT6), an NAD-dependent deacetylase, is known to promote metastasis of non-small cell lung cancer (NSCLC).

methodsIn this work, we determined the role of SIRT6 in the EMT of NSCLC cells and identified the key EMT-related genes involved in the oncogenic activity of SIRT6.

resultsWe report that depletion of SIRT6 inhibits transforming growth factor-β1 (TGF-β1)-induced EMT in A549 and H1299 NSCLC cells, which is rescued by ectopic expression of SIRT6. Knockdown of SIRT6 leads to a reduction in Snail protein without affecting the mRNA level. Immunoprecipitation experiments demonstrate a physical association between SIRT6 and Snail. SIRT6 deacetylates Snail and prevents its proteasomal degradation. Silencing of Snail blunts SIRT6-induced NSCLC cell migration and invasion, while overexpression of Snail restores the invasion and EMT in SIRT6-depleted NSCLC cells. SIRT6 depletion leads to an upregulation of kruppel-like factor 4 (KLF4) and reduced Snail binding to the promoter of Klf4 in NSCLC cells. Knockdown of KLF4 rescues the invasive capacity in SIRT6-depleted NSCLC cells. Conversely, co-expression of KLF4 impairs SIRT6-induced aggressive behavior. In vivo data further demonstrate that SIRT6-induced NSCLC metastasis is antagonized by overexpression of KLF4.

conclusionsThese findings provide mechanistic insights into the pro-metastatic activity of SIRT6 and highlight the role of the SIRT6/Snail/KLF4 axis in regulating EMT and invasion of NSCLC cells.

Indexed as

A549 CellsAnimalsCarcinoma, Non-Small-Cell LungEpithelial-Mesenchymal TransitionHeterograftsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsLung NeoplasmsMaleMiceMice, NudeNeoplasm InvasivenessSirtuinsTransfectionTransforming Growth Factor beta1KLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsSIRT6 protein, humanSirtuinsTransforming Growth Factor beta1Lung cancerMetastasisSIRT6SnailTransrepress

Identifiers

PMID30577808
PMCPMC6303940
OpenAlexW2906071128

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.