Evidence map›Paper›PMID 39061061›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

SLC14A1 and TGF-β signaling: a feedback loop driving EMT and colorectal cancer metachronous liver metastasis.

Yixun Zhang, Yumeng Yang, Xuan Qi, Peng Cui, Yi Kang, Haiyi Liu, Zhigang Wei, Haibo Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

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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

8 authors.

Yixun Zhang *Department of Colorectal Surgery, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, China.
Yumeng Yang *Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
Xuan Qi *Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
Peng CuiDepartment of General Surgery, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Yi KangDepartment of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, China.
Haiyi LiuDepartment of Colorectal Surgery, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, China.
Zhigang WeiHepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, 85 Jiefang Nan Lu, Taiyuan, 030001, Shanxi, China. wzgsyyy@163.com.
Haibo WangDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, 100069, China. haiba-110@ccmu.edu.cn.ORCID http://orcid.org/0000-0003-1902-5251

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) metachronous liver metastasis is a significant clinical challenge, largely attributable to the late detection and the intricate molecular mechanisms that remain poorly understood. This study aims to elucidate the role of Solute Carrier Family 14 Member 1 (SLC14A1) in the pathogenesis and progression of CRC metachronous liver metastasis.

methodsWe conducted a comprehensive analysis of CRC patient data from The Cancer Genome Atlas and GSE40967 databases, focusing on the differential expression of genes associated with non-metachronous liver metastasis and metachronous liver metastasis. Functional assays, both in vitro and in vivo, were performed to assess the biological impact of SLC14A1 modulation in CRC cells. Gene set enrichment analysis, molecular assays and immunohistochemical analyses on clinical specimens were employed to unravel the underlying mechanisms through which SLC14A1 exerts its effects.

resultsSLC14A1 was identified as a differentially expressed gene, with its overexpression significantly correlating with poor relapse-free and overall survival. Mechanistically, elevated SLC14A1 levels enhanced CRC cell invasiveness and migratory abilities, corroborated by upregulated TGF-β/Smad signaling and Epithelial-Mesenchymal Transition. SLC14A1 interacted with TβRII and stabilized TβRII protein, impeding its Smurf1-mediated K48-linked ubiquitination and degradation, amplifying TGF-β/Smad signaling. Furthermore, TGF-β1 reciprocally elevated SLC14A1 mRNA expression, with Snail identified as a transcriptional regulator, binding downstream of SLC14A1's transcription start site, establishing a positive feedback loop. Clinically, SLC14A1, phosphorylated Smad2, and Snail were markedly upregulated in CRC patients with metachronous liver metastasis, underscoring their potential as prognostic markers.

conclusionsOur findings unveil SLC14A1 as a critical regulator in CRC metachronous liver metastasis, providing novel insights into the molecular crosstalk between SLC14A1 and TGF-β/Smad signaling. These discoveries not only enhance our understanding of CRC metachronous liver metastasis pathogenesis, but also highlight SLC14A1 as a promising target for therapeutic intervention and predictive marker.

Indexed as

Colorectal NeoplasmsEpithelial-Mesenchymal TransitionLiver NeoplasmsSignal TransductionTransforming Growth Factor betaAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMicePrognosisUrea TransportersSLC14A1 protein, humanTransforming Growth Factor betaUrea TransportersColorectal cancerMetachronous liver metastasisSLC14A1TGF-β/Smad signaling

Identifiers

PMID39061061
PMCPMC11282742

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Registered trials

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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.