Evidence map›Paper›PMID 26028023›Full record

ArticleOncogene2016

The matricellular protein CCN1 suppresses hepatocarcinogenesis by inhibiting compensatory proliferation.

C-C Chen, K-H Kim, L F Lau

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

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
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  16. Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  17. Article
  18. Article
  19. The matricellular protein CCN1 in tissue injury repair.Journal of cell communication and signaling · 2018
    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

3 authors at 1 institution in 1 country.

C-C ChenDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
K-H KimDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
L F LauDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
University of Illinois Chicago · US

Funding

Regulation of TNF-alpha by Integrin-Mediated Matrix SignalingR01GM078492 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LAU, LESTER F · 2007 to 2018
$4.3M
The Matricellular Protein CCN1 in Wound HealingR01AR061791 · NIAMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LAU, LESTER F · 2011 to 2021
$3.8M
NIAMS NIH HHS R01 AR061791NIGMS NIH HHS R01 GM078492NIGMS NIH HHS R01GM78492
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is on the rise in the United States. Previous studies showed that the matricellular protein CCN1 (CYR61) is induced during hepatic injuries and functions to restrict and resolve liver fibrosis. Here, we show that CCN1 suppresses hepatocarcinogenesis by inhibiting carcinogen-induced compensatory hepatocyte proliferation, thus limiting the expansion of damaged and potentially oncogenic hepatocytes. Consistent with tumor suppression, CCN1 expression is downregulated in human HCC. Ccn1(ΔHep) mice with hepatocyte-specific deletion of Ccn1 suffer increased HCC tumor multiplicity induced by the hepatocarcinogen diethylnitrosamine (DEN). Knockin mice (Ccn1(dm/dm)) that express an integrin α6β1-binding defective CCN1 phenocopied Ccn1(ΔHep) mice, indicating that CCN1 acts through its α6β1 binding sites in this context. CCN1 effectively inhibits epidermal growth factor receptor (EGFR)-dependent hepatocyte proliferation through integrin α6-mediated accumulation of reactive oxygen species (ROS), thereby triggering p53 activation and cell cycle block. Consequently, Ccn1(dm/dm) mice exhibit diminished p53 activation and elevated compensatory hepatocyte proliferation, resulting in increased HCC. Furthermore, we show that a single dose of the EGFR inhibitor erlotinib delivered prior to DEN-induced injury was sufficient to block compensatory proliferation and annihilate development of HCC nodules observed 8 months later, suggesting potential chemoprevention by targeting CCN1-inhibitable EGFR-dependent hepatocyte proliferation. Together, these results show that CCN1 is an injury response protein that functions not only to restrict fibrosis in the liver, but also to suppress hepatocarcinogenesis by inhibiting EGFR-dependent hepatocyte compensatory proliferation.

Indexed as

AnimalsCarcinogenesisCarcinoma, HepatocellularCell Line, TumorCell ProliferationCysteine-Rich Protein 61DiethylnitrosamineErbB ReceptorsGene Expression Regulation, NeoplasticHumansLiverLiver NeoplasmsMaleMiceMice, Inbred C57BLMutationCysteine-Rich Protein 61DiethylnitrosamineEGFR protein, humanErbB Receptorsp38 Mitogen-Activated Protein KinasesReactive Oxygen SpeciesTumor Suppressor Protein p53

Identifiers

PMID26028023
PMCPMC4666840
OpenAlexW1522378176

What OpenQuestion holds

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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.