Evidence map›Paper›PMID 35022331›Full record

ArticleAging2022

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer.

Guolin Zhang, Xin Luo, Zian Wang, Jianbin Xu, Wei Zhang, Engeng Chen, Qing Meng, Di Wang, Xuefeng Huang, Wei Zhou and 1 more

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

Article in Aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-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

14 citing papers in PubMed, 28 citations in OpenAlex.

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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

11 authors at 4 institutions in 1 country.

Guolin ZhangDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Xin LuoDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Zian WangDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Jianbin XuZhejiang Province Key Laboratory of Biological Treatment, Hangzhou, China.
Wei ZhangDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Engeng ChenDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Qing MengDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Di WangDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Xuefeng HuangDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Wei ZhouDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Zhangfa SongDepartment of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.
Sir Run Run Shaw Hospital · CNZhejiang University · CNBlood Center of Zhejiang Province · CNShaoxing People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

5-Fluorouracil (5-Fu) is the first-line chemotherapeutic option for colorectal cancer. However, its efficacy is inhibited by drug resistance. Cytokines play an important role in tumor drug resistance, even though their mechanisms are largely unknown. Using a cytokine array, we established that tissue inhibitor metalloproteinase 2 (TIMP-2) is highly expressed in 5-Fu resistant colorectal cancer patients. Analysis of samples from 84 patients showed that elevated TIMP-2 expression levels in colorectal patients were correlated with poor prognostic outcomes. In a 5-Fu-resistant patient-derived xenograft (PDX) model, TIMP-2 was also found to be highly expressed. We established an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients. In conclusion, a novel TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism is involved in colorectal cancer. Therefore, targeting TIMP-2 or ERK/MAPK may provide a new strategy to overcome 5-Fu resistance in colorectal cancer chemotherapy.

Indexed as

Drug Resistance, NeoplasmAgedAnimalsButadienesCell SurvivalColorectal NeoplasmsCytokinesExtracellular Signal-Regulated MAP KinasesFemaleFluorouracilGene Expression Regulation, NeoplasticHumansMaleMAP Kinase Signaling SystemMiceMice, NudeButadienesCytokinesExtracellular Signal-Regulated MAP KinasesFluorouracilNitrilesTIMP2 protein, humanTissue Inhibitor of Metalloproteinase-2U 01265-Fucolorectal cancerdrug resistanceERK/MAPK signaling pathwayTIMP-2

Identifiers

PMID35022331
PMCPMC8791226
OpenAlexW4225410764

What OpenQuestion holds

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LicenceCC BY
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.