Evidence map›Paper›PMID 40234387›Full record

ArticleCell death & disease2025

CCN1 is a therapeutic target upregulated in EML4-ALK mutant lung adenocarcinoma reversibly resistant to alectinib.

Yihua Huang, Jie Huang, Jianhua Zhan, Maojian Chen, Jiani Zheng, Junyi He, Wenfeng Fang, Li Zhang, Jing Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

  1. Article
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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

9 authors.

Yihua Huang *Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
Jie Huang *Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
Jianhua Zhan *Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
Maojian Chen *Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Jiani ZhengDepartment of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Junyi HeDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
Wenfeng FangDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China. fangwf@sysucc.org.cn.
Li ZhangDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China. zhangli@sysucc.org.cn.ORCID http://orcid.org/0000-0003-0595-0761
Jing LiDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China. lijing3@sysucc.org.cn.ORCID http://orcid.org/0000-0001-5697-9527

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There is limited understanding of the phenomenon of reversible drug resistance, which is characterized by tumor cells regaining sensitivity when the drug is changed or withdrawn after a period of drug resistance. This phenomenon is usually not associated with genetic alterations of tumor cells. In this study, reversible resistant state was induced by alectinib in EML4-ALK mutant lung cancer cell. By performing RNA sequencing on reversible drug-resistant cell line to examine changes in transcriptional profile, significant change in CCN1 was detected after withdrawal and repeated administration of alectinib. Targeting CCN1 resulted in inhibition of tumor cell proliferation and angiogenesis, and restoration of sensitivity to alectinib in reversible drug-resistant cells. Further studies revealed that CCN1 could affect the expression of VEGFA by affecting AKT phosphorylation, and the change of NF-κB could impact the activation of CCN1-AKT-VEGFA pathway. Suppressing NF-κB or CCN1 receptor could improve the sensitivity to alectinib, further suggesting that NF-κB and CCN1 might play a key role in overcoming reversible drug resistance.

Indexed as

Adenocarcinoma of LungCarbazolesCysteine-Rich Protein 61Drug Resistance, NeoplasmLung NeoplasmsOncogene Proteins, FusionPiperidinesAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMiceMutationNF-kappa BProto-Oncogene Proteins c-aktalectinibCarbazolesCCN1 protein, humanCysteine-Rich Protein 61EML4-ALK fusion protein, humanNF-kappa BOncogene Proteins, FusionPiperidinesProto-Oncogene Proteins c-aktVascular Endothelial Growth Factor A

Identifiers

PMID40234387
PMCPMC12000322

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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.