Evidence map›Paper›PMID 41285809›Full record

ArticleCell death & disease2025

Targeting CREB3L2-mediated lipid metabolism overcomes lenvatinib resistance and attenuates the progression of hepatocellular carcinoma.

Shiguang Yang, Shaoqing Liu, Jie Li, Shengwei Mao, Qifeng Yu, Xuhui Zhao, Xiaoling Wu, Jiafeng Chen, Yichao Bu, Weiren Liu and 2 more

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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Shiguang Yang *Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, China.
Shaoqing Liu *Department of Breast Surgery, Department of Emergency Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Jie Li *National Medical Center & National Clinical Research Center for Interventional Medicine, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Shengwei MaoDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Qifeng YuDepartment of Hepatobiliary Surgery, Zhoushan Hospital, Zhejiang, China.ORCID http://orcid.org/0000-0001-9953-988X
Xuhui ZhaoDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaoling WuDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Jiafeng ChenDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Yichao BuDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0002-1283-3547
Weiren LiuDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. liu.weiren@zs-hospital.sh.cn.ORCID http://orcid.org/0000-0003-3393-1322
Yuan FangDepartment of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. fangyuan1029@126.com.ORCID http://orcid.org/0009-0006-7342-4877
Yinghong ShiDepartment of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, China. shi.yinghong@zs-hospital.sh.cn.ORCID http://orcid.org/0000-0002-1833-8988

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

When hepatocellular carcinoma (HCC) cells exhibit malignant biological behaviors, lipid metabolic reprogramming occurs concomitantly. Thus, identifying regulators of metabolic reprogramming offers new potential targets for therapy. In this study, we investigated the mechanisms by which Cyclic adenosine monophosphate-responsive element binding protein 3-like 2(CREB3L2) influences HCC progression and contributes to lenvatinib resistance through modulation of lipid metabolism. Up-regulated expression of CREB3L2 was observed in numerous HCC cohorts and associated with poor survival prognosis of patients. Furthermore, CREB3L2 could facilitate the proliferation and metastatic capacity of HCC cells both in vitro and in vivo. It was found that CREB3L2 influences the proliferation and metastasis of HCC cells by up-regulating sterol regulatory element binding protein 1 (SREBP1), a vital regulatory factor of lipid synthesis for fatty acid production. Additionally, CREB3L2 enhances SREBP1 protein expression and stability through increased acetylation mediated by histone acetyltransferase-1(HAT1). Importantly, targeting CREB3L2 in combination with lenvatinib significantly reduced lenvatinib resistance, inhibiting the progression of CREB3L2 high-expressing HCC tumors. These findings suggest that the CREB3L2/HAT1/SREBP1 regulatory axis drives lenvatinib resistance and HCC progression by impacting lipid metabolism. Targeting CREB3L2 alongside lenvatinib improves the efficacy of treating HCC.

Indexed as

Carcinoma, HepatocellularCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmLipid MetabolismLiver NeoplasmsPhenylurea CompoundsQuinolinesAnimalsCell Line, TumorCell ProliferationDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMaleMiceCyclic AMP Response Element-Binding ProteinlenvatinibPhenylurea CompoundsQuinolinesSREBF1 protein, humanSterol Regulatory Element Binding Protein 1

Identifiers

PMID41285809
PMCPMC12644697

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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.