Evidence map›Paper›PMID 40616024›Full record

ArticleBMC cancer2025

S100a4 promotes metastatic transformation in non-metastatic liver cancer cells through NMIIa binding: mechanistic insights.

Yong Qin, Chaojun Wang, Shengqian Xu, Junbin Zhou, Shimiao Li, Hailin Ye

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PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

3 citing papers in PubMed.

  1. Review
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4 · The record

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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

6 authors.

Yong QinDepartment of Hepatobiliary Pancreatic Surgery, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, No. 15 Dazhong road, Lishui, Zhejiang, 323000, China.
Chaojun WangDepartment of Ultrasound, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, No. 15 Dazhong road, Lishui, Zhejiang, 323000, China.
Shengqian XuDepartment of Hepatobiliary Pancreatic Surgery, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, No. 15 Dazhong road, Lishui, Zhejiang, 323000, China.
Junbin ZhouDepartment of Hepatobiliary Pancreatic Surgery, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, No. 15 Dazhong road, Lishui, Zhejiang, 323000, China.
Shimiao LiDepartment of Hepatobiliary Pancreatic Surgery, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, No. 15 Dazhong road, Lishui, Zhejiang, 323000, China.
Hailin YeDepartment of Hepatobiliary Pancreatic Surgery, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, No. 15 Dazhong road, Lishui, Zhejiang, 323000, China. 18957092785@163.com.

Funding

Lishui City self-funded public welfare technology application research project No. 2022SJZC030Zhejiang basic public welfare research project, Project Category: Social Development No. LGF22H160059Zhejiang Provincial Medical and Health Science and Technology Program Project, Project category: General Project No. 2024KY581
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors, characterized by high recurrence and metastasis rates. Studies have demonstrated that exosomes, as signaling mediators between tumor cells and their microenvironment, play crucial roles in tumor cell migration and invasion. S100A4, a known metastasis-associated protein, has been identified as a key factor in promoting cancer cell migration and epithelial-mesenchymal transition (EMT).

methodsTo investigate the relationship between S100A4 and high metastasis in HCC, we performed analyses using TCGA-HCC data and clinical samples. Stable HCC cell lines overexpressing S100A4 were established to evaluate S100A4 expression levels among various HCC cell types. The migration and invasion capabilities of these cells were assessed using wound healing and Transwell assays. Additionally, Western blotting, qPCR, and immunohistochemistry (IHC) were employed to detect changes in EMT-related markers and NMIIA expression following S100A4 overexpression.

resultsData from TCGA and IHC analyses revealed that S100A4 is highly expressed in HCC patients and that its elevated expression correlates with lymph node metastasis and advanced tumor stage. High S100A4-expressing (S100A4^H) HCC cells (JHH-1 and Li-7) exhibited enhanced migratory and invasive capabilities, whereas low S100A4-expressing cells (Huh-7 and Hep G2) displayed weaker metastatic characteristics. Exosomes derived from S100A4^H cells also showed elevated levels of S100A4. Overexpression of S100A4 in HCC cells promoted cell migration, invasion, and viability. Moreover, exosomes derived from S100A4^H cells significantly enhanced the migration and invasion of co-cultured HCC cells. Mechanistically, S100A4 overexpression significantly downregulated E-cadherin expression while upregulating Twist1, N-cadherin, and Vimentin levels. Notably, S100A4 formed a complex with NMIIA in HCC cells, and NMIIA silencing suppressed S100A4-induced changes in EMT-related protein expression.

conclusionS100A4 promotes HCC cell migration, invasion, and metastasis by activating the EMT process via NMIIA, potentially through exosome-mediated signaling. S100A4 may serve as a potential biomarker for predicting EMT occurrence, disease progression, and prognosis in HCC patients.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsS100 Calcium-Binding Protein A4Cell Line, TumorCell MovementEpithelial-Mesenchymal TransitionExosomesFemaleGene Expression Regulation, NeoplasticHumansMaleNeoplasm InvasivenessNeoplasm MetastasisS100A4 protein, humanS100 Calcium-Binding Protein A4Epithelial-mesenchymal transitionExosomesHepatocellular carcinomaNon-muscle myosin IIAS100A4

Identifiers

PMID40616024
PMCPMC12228176

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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.