Evidence map›Paper›PMID 25893304›Full record

ArticleOncogene2015

Lysine-specific demethylase 1 promotes the stemness and chemoresistance of Lgr5(+) liver cancer initiating cells by suppressing negative regulators of β-catenin signaling.

Z-J Lei, J Wang, H-L Xiao, Y Guo, T Wang, Q Li, L Liu, X Luo, L-L Fan, L Lin and 9 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

65 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Review
  3. Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025
    Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Aberrant RNA mCell death & disease · 2023
    Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 2 countries.

Z-J LeiDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
J WangDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
H-L XiaoDepartment of Pathology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Y GuoDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
T WangDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Q LiDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
L LiuDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
X LuoDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
L-L FanDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
L LinDepartment of Pathology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
C-Y MaoDepartment of Pathology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
S-N WangDepartment of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Y-L WeiDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
C-H LanDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
J JiangDepartment of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
X-J YangCenter for Neuroscience, Shantou University Medical College, Shantou, China.
P-D LiuDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
D-F ChenDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.ORCID 0000000155741760
B WangDepartment of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Army Medical University · CNBeth Israel Deaconess Medical Center · USShantou University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer initiating cells (CICs) are responsible for the unrestrained cell growth and chemoresistance of malignant tumors. Histone demethylation has been shown to be crucial for self-renewal/differentiation of stem cells, but it remains elusive whether lysine-specific demethylase 1 (LSD1) regulates the stemness properties of CICs. Here we report that the abundant expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is associated with the progression of hepatocellular carcinoma (HCC). Lgr5(+) HCC cells behave similarly to CICs and are highly tumorigenic and resistant to chemotherapeutic agents. Importantly, Lgr5(+) cells express higher levels of LSD1, which in turn regulates Lgr5 expression and promotes the self-renewal and drug resistance of Lgr5(+) CICs. Mechanistically, LSD1 promotes β-catenin activation by inhibiting the expression of several suppressors of β-catenin signaling, especially Prickle1 and APC in Lgr5(+) CICs, by directly regulating the levels of mono- and di-methylation of histone H3 lysine-4 at the promoters of these genes. Furthermore, LSD1-associated activation of the β-catenin signaling is essential for maintaining the activity of Lgr5(+) CICs. Together, our findings unravel the LSD1/Prickle1/APC/β-catenin signaling axis as a novel molecular circuit regulating the stemness and chemoresistance of hepatic Lgr5(+) CICs and provide potential targets to improve chemotherapeutic efficacies against HCC.

Indexed as

Animalsbeta CateninCarcinoma, HepatocellularDown-RegulationDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHistone DemethylasesHumansLiver NeoplasmsMaleMiceMice, NudeNeoplastic Stem CellsReceptors, G-Protein-CoupledTumor Cells, CulturedWnt Signaling Pathwaybeta CateninHistone DemethylasesKDM1A protein, humanLGR5 protein, humanReceptors, G-Protein-Coupled

Identifiers

PMID25893304
OpenAlexW2070287368

What OpenQuestion holds

Textmetadata
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.