Evidence map›Paper›PMID 40804742›Full record

ArticleJournal of translational medicine2025

Cancer cell SPOCD1 promotes colorectal cancer liver metastasis by activating the CXCL12/CXCR4 signaling pathway in cancer-associated fibroblasts.

Geng Peng, Lin Zhong, Lina Luo, Yongle Ju, Yan Lu, Lui Ng, Dominic Chi-Chung Foo, Fu Cheng, Luji Huang, Manzhao Ouyang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026
    Review
  3. Review
  4. Review
  5. 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

10 authors.

Geng Peng *Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Lin Zhong *Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Lina Luo *Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Yongle JuDepartment of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Yan LuGCP Center, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Lui NgDepartment of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Dominic Chi-Chung FooDepartment of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Fu ChengDepartment of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Luji HuangDepartment of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
Manzhao OuyangDepartment of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China. doctorken@smu.edu.cn.ORCID 0009-0004-6308-5248

Funding

Guangdong Provincial Basic and Applied Basic Research Fund Mindray Joint Fund Project No.2023A1515220149Southern Medical University Shunde Hospital 2022 Research Initiation Programme Project No.SRSP2022006Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project No.SRSP2023016
6 · The paper itself

Abstract

backgroundLiver metastasis remains a major cause of death in colorectal cancer (CRC). Interactions between tumor cells and components of the tumor microenvironment (TME) are integral to the progression of cancer cell migration and metastatic dissemination. Investigating these cellular dynamics is essential for identifying actionable therapeutic targets.

methodsThis study employed bioinformatics analysis, IHC, WB, and murine in vivo imaging to delineate the role of SPOCD1 in CRC. Additional in vitro co-culture systems, immunofluorescence, and RNA-seq were utilized to determine how SPOCD1 modulated epithelial-mesenchymal transition (EMT) through cancer-associated fibroblasts (CAFs). Mechanistic insight into SPOCD1-mediated transcriptional regulation of LAMA4 was obtained via dual-luciferase reporter assays, ChIP-qPCR, and Co-IP.

resultsSPOCD1 was found to be markedly upregulated in CRC cells and exhibited potent pro-metastatic activity in vivo. Integration of external datasets with experimental validation revealed a strong correlation between SPOCD1 expression and CAFs infiltration in the TME. Further analyses demonstrated that SPOCD1 enhanced CXCL12 expression in CAFs via upregulation of LAMA4, enabling CXCL12 to engage CXCR4 on CRC cells and activate EMT signaling, thereby driving metastasis. This signaling axis was effectively interrupted by CXCR4 inhibitors. Mechanistically, SPOCD1 promoted LAMA4 expression through DNMT1 recruitment, facilitating DNA methylation-dependent transcriptional regulation.

conclusionThis study delineates a SPOCD1-centered interaction network between CRC cells and CAFs in colorectal cancer liver metastasis (CRLM), offering novel molecular candidates for therapeutic intervention in CRLM.

Indexed as

Cancer-Associated FibroblastsChemokine CXCL12Colorectal NeoplasmsLiver NeoplasmsReceptors, CXCR4Signal TransductionAnimalsCell Line, TumorCell MovementEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansLamininMiceTumor MicroenvironmentUp-RegulationChemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanLamininReceptors, CXCR4Cancer-associated fibroblastsColorectal cancerEpithelial-to-mesenchymal transitionLiver metastasisSPOCD1

Identifiers

PMID40804742
PMCPMC12351940

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.