Evidence map›Paper›PMID 32512510›Full record

ArticleEBioMedicine2020

Organoid modelling identifies that DACH1 functions as a tumour promoter in colorectal cancer by modulating BMP signalling.

Xiang Hu, Long Zhang, Yaqi Li, Xiaoji Ma, Weixing Dai, Xiaoxue Gao, Xinxin Rao, Guoxiang Fu, Renjie Wang, Mengxue Pan and 8 more

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

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Homer condensates orchestrate YAP-Wnt signaling crosstalk downstream of the Crumbs polarity complex.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  7. Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
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  10. CRISPR/Cas9: a powerful tool in colorectal cancer research.Journal of experimental & clinical cancer research : CR · 2023
    Review
  11. Review
  12. Article
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  14. Review
  15. Article
  16. Application Progress of Organoids in Colorectal Cancer.Frontiers in cell and developmental biology · 2022
    Review
  17. Review
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  19. Review
  20. Article
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

18 authors at 2 institutions in 1 country.

Xiang HuDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Long ZhangDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Yaqi LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Xiaoji MaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Weixing DaiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Xiaoxue GaoInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Xinxin RaoInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Guoxiang FuInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Renjie WangDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Mengxue PanInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Qiang GuoInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Xiaoya XuInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Yi ZhouInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Jianjun GaoInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Zhen ZhangDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Sanjun CaiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China. Electronic address: caisanjun_sh@163.com.
Junjie PengDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: pengjj67@hotmail.com.
Guoqiang HuaInstitute of Radiation Medicine, and Cancer institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China. Electronic address: guoqianghua@fudan.edu.cn.
Fudan University Shanghai Cancer Center · CNShanghai Medical College of Fudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDachshund homologue 1 (DACH1) is highly expressed in LGR5+ intestinal stem cells and colorectal tumours. However, the roles of DACH1 in intestinal cell stemness and colorectal tumorigenesis remain largely undefined.

methodsWe used immunohistochemistry, western blotting and quantitative real-time PCR to analyse DACH1 expression in colorectal cancer (CRC) samples. CRISPR/Cas9 gene editing and lentiviral vector-mediated overexpression and shRNA-mediated knockdown of DACH1 were utilized to modulate DACH1 expression in cell lines and organoids. An intestinal organoid-based functional model was analysed, and cancer cell colony formation, sphere formation assays and murine xenotransplants were performed to reveal the role of DACH1 in CRC cell proliferation, stemness and tumorigenesis. Immunofluorescence, co-immunoprecipitation, RNA interference and microarray data analyses were conducted to demonstrate the association between DACH1 and the bone morphogenetic protein (BMP) signalling pathway.

findingsDACH1 is specifically expressed in discrete crypt base cells, and increased DACH1 expression was found in all stages of CRC. Moreover, the high expression of DACH1 independently predicted poor prognosis. In colon cancer cells, shRNA-mediated suppression of DACH1 inhibited cell growth in vitro and in vivo. By studying the intestinal organoid-based functional model, we found that depletion of DACH1 reduced the organoid formation efficiency and tumour organoid size. DACH1 overexpression stimulated both colonsphere formation and tumour organoid formation in the context of dysregulated BMP signalling. Mechanistic characterizations indicated that overexpression of DACH1 affects a subset of stem cell signature genes implicated in stem cell proliferation and maintenance through the suppression of BMP signalling via SMAD4.

interpretationTogether, our study highlights DACH1 as an integral regulator of BMP signalling during intestinal tumorigenesis, and DACH1 could be a potential prognostic marker and therapeutic target for colorectal cancer patients.

Indexed as

Up-RegulationAgedAnimalsBone Morphogenetic ProteinsCell Line, TumorCell ProliferationColorectal NeoplasmsEpithelial-Mesenchymal TransitionEye ProteinsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHumansMaleMiceMiddle AgedBone Morphogenetic ProteinsDACH1 protein, humanEye ProteinsTranscription FactorsBMP signalling pathwayColorectal cancerDACH1OrganoidStem cells

Identifiers

PMID32512510
PMCPMC7281795
OpenAlexW3033861388

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.