Evidence map›Paper›PMID 28415588›Full record

ArticleOncotarget2017

Smad inhibitor induces CSC differentiation for effective chemosensitization in cyclin D1- and TGF-β/Smad-regulated liver cancer stem cell-like cells.

Wei Xia, Chung Mau Lo, Randy Y C Poon, Tan To Cheung, Albert C Y Chan, Lin Chen, Sitian Yang, George S W Tsao, Xiao Qi Wang

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.9field-weighted citation impact, top 7% 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

42 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Effects of Ultra-Short Pulsed Electric Field Exposure on Glioblastoma Cells.International journal of molecular sciences · 2022
    Article
  20. Review
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

9 authors at 1 institution in 1 country.

Wei XiaDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
Chung Mau LoDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
Randy Y C PoonDivision of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
Tan To CheungDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
Albert C Y ChanDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
Lin ChenDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
Sitian YangDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
George S W TsaoSchool of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.
Xiao Qi WangDepartment of Surgery, The University of Hong Kong, Hong Kong, China.
University of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding cancer stem cell (CSC) maintenance pathways is critical for the development of CSC-targeting therapy. Here, we investigated the functional role of the cyclin D1-dependent activation of Smad2/3 and Smad4 in hepatocellular carcinoma (HCC) CSCs and in HCC primary tumors. Cyclin D1 sphere-derived xenograft tumor models were employed to evaluate the therapeutic effects of a Smad inhibitor in combination with chemotherapy. Cyclin D1 overexpression confers stemness properties by enhancing single sphere formation, enhancing the CD90+ and EpCAM+ population, increasing stemness gene expression, and increasing chemoresistance. Cyclin D1 interacts with and activates Smad2/3 and Smad4 to result in cyclin D1-Smad2/3-Smad4 signaling-regulated liver CSC self-renewal. The cyclin D1-dependent activation of Smad2/3 and Smad4 is also found in HCC patients and predicts disease progression. A Smad inhibitor impaired cyclin D1-Smad-mediated self-renewal, resulting in the chemosensitization. Thus, pretreatment with a Smad inhibitor followed by chemotherapy not only successfully suppressed tumor growth but also eliminated 57% of the tumors in a cyclin D1 sphere-derived xenograft model. Together, The cyclin D1-mediated activation of Smad2/3 and Smad4 is an important regulatory mechanism in liver CSC self-renewal and stemness. Accordingly, a Smad inhibitor induced CSC differentiation and consequently significant chemosensitization, which could be an effective strategy to target CSCs.

Indexed as

Drug Resistance, NeoplasmAnimalsAntineoplastic AgentsApoptosisBiomarkers, TumorCarcinoma, HepatocellularCell DifferentiationCell ProliferationCyclin D1HumansLiver NeoplasmsMaleMiceMice, SCIDNeoplastic Stem CellsPrognosisAntineoplastic AgentsBiomarkers, TumorCCND1 protein, humanCyclin D1Smad2 ProteinSMAD2 protein, humanSmad4 ProteinSMAD4 protein, humanTransforming Growth Factor betacancer stem cellschemosensitizationcyclin D1Smad2/3/Smad4Smad inhibitor

Identifiers

PMID28415588
PMCPMC5503574
OpenAlexW2598725325

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.