Evidence map›Paper›PMID 32398865›Full record

ArticleOncogene2020

LAMB3 promotes tumour progression through the AKT-FOXO3/4 axis and is transcriptionally regulated by the BRD2/acetylated ELK4 complex in colorectal cancer.

Zhehui Zhu, Jinglue Song, Yuegui Guo, Zhenyu Huang, Xiaojian Chen, Xuening Dang, Yuji Huang, Yuhan Wang, Weijun Ou, Yili Yang and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

42 citing papers in PubMed, 90 citations in OpenAlex.

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  20. Cellulose nanofibril matrix drives the dynamic formation of spheroids.Journal of Zhejiang University. Science. B · 2023
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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

13 authors at 5 institutions in 1 country.

Zhehui Zhu *Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
Jinglue Song *Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
Yuegui Guo *Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
Zhenyu HuangShanghai Colorectal Cancer Research Center, 200092, Shanghai, China.
Xiaojian ChenShanghai Colorectal Cancer Research Center, 200092, Shanghai, China.
Xuening DangShanghai Colorectal Cancer Research Center, 200092, Shanghai, China.
Yuji HuangShanghai Colorectal Cancer Research Center, 200092, Shanghai, China.
Yuhan WangDepartment of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
Weijun OuDepartment of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
Yili YangSuzhou Institute of Systems Medicine, Center for Systems Medicine Research, Chinese Academy of Medical Sciences, 215123, Suzhou, Jiangsu, China.
Wei YuState Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Zhongshan Hospital, Fudan University, 200438, Shanghai, China. yuw@fudan.edu.cn.ORCID http://orcid.org/0000-0001-9898-4607
Chen-Ying LiuDepartment of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China. liuchenying@xinhuamed.com.cn.ORCID http://orcid.org/0000-0002-8930-6182
Long CuiDepartment of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China. cuilong@xinhuamed.com.cn.ORCID http://orcid.org/0000-0003-1838-4471
Shanghai Jiao Tong University · CNShanghai Cancer Institute · CNXinHua Hospital · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNFudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant expression of laminin-332 promotes tumour growth and metastasis in multiple cancers. However, the dysregulated expression and mechanism of action of LAMB3, which encodes the β3 subunit of laminin-332, and the mechanism underlying dysregulated LAMB3 expression in CRC remain obscure. Here, we show that LAMB3 is overexpressed in CRC and that this overexpression is correlated with tumour metastasis and poor prognosis. Overexpression of LAMB3 promoted cell proliferation and cell migration in vitro and tumour growth and metastasis in vivo, while knockdown of LAMB3 elicited opposing effects. LAMB3 inhibited the tumour suppressive function of FOXO3/4 by activating AKT in CRC. Both the BET inhibitor JQ1 and the MEK inhibitor U0126 decreased the mRNA level of LAMB3 in multiple CRC cells. Mechanistically, ELK4 cooperated with BRD2 to regulate the transcription of LAMB3 in CRC by directly binding to the ETS binding motifs in the LAMB3 promoter. ELK4 was as acetylated at K125, which enhanced the interaction between ELK4 and BRD2. JQ1 disrupted the interaction between ELK4 and BRD2, resulting in decreased binding of BRD2 to the LAMB3 promoter and downregulation of LAMB3 transcription. Both ELK4 and BRD2 expression was associated with LAMB3 expression in CRC. LAMB3 expression was also negatively correlated with FOXO3/4 in CRC. Our study reveals the pro-tumorigenic role of LAMB3 through the AKT-FOXO3/4 axis and the transcriptional mechanism of LAMB3 in CRC, demonstrating that LAMB3 is a potential therapeutic target that can be targeted by BET inhibitors and MEK inhibitors.

Indexed as

Signal TransductionAcetylationAnimalsBromodomain Containing ProteinsCell Adhesion MoleculesCell Cycle ProteinsColorectal Neoplasmsets-Domain Protein Elk-4FemaleForkhead Box Protein O3Forkhead Transcription FactorsHumansKalininMaleMiceProto-Oncogene Proteins c-aktBRD2 protein, humanBromodomain Containing ProteinsCell Adhesion MoleculesCell Cycle ProteinsELK4 protein, humanets-Domain Protein Elk-4Forkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanFOXO4 protein, humanKalininProto-Oncogene Proteins c-aktTranscription Factors

Identifiers

PMID32398865
OpenAlexW3025976096

What OpenQuestion holds

Textmetadata
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.