Evidence map›Paper›PMID 39718738›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2024

GALNT6 drives lenvatinib resistance in hepatocellular carcinoma through autophagy and cancer-associated fibroblast activation.

Peiling Zhang, Shiping Chen, Jialiang Cai, Lina Song, Bing Quan, Jinglei Wan, Guiqi Zhu, Biao Wang, Yi Yang, Zhengjun Zhou and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. GALNT1 emerges as a potential therapeutic target in breast cancer.Journal of cancer research and clinical oncology · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
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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

12 authors.

Peiling Zhang *Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shiping Chen *Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jialiang Cai *Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Lina SongLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Bing QuanLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jinglei WanLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Guiqi ZhuLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Biao WangDepartments of Radiation Oncology Zhongshan Hospital, Fudan University, Shanghai, China.
Yi YangDepartments of Radiation Oncology Zhongshan Hospital, Fudan University, Shanghai, China.
Zhengjun ZhouLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Tao LiDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. transplant@126.com.
Zhi DaiLiver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. dai.zhi@zs-hospital.sh.cn.

Funding

Natural Science Foundation of China 82372946the Leading Project of the Science and Technology Committee of Shanghai Municipality 21Y21900100the Project of Shanghai Municipal Health Commission 202140269
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) remains a significant global health challenge with limited treatment options. Lenvatinib, a tyrosine kinase inhibitor, has shown promise but is often undermined by the development of drug resistance.

methodsUtilizing high-throughput sequencing, we investigated the molecular mechanisms underlying lenvatinib resistance in HCC cells, with a focus on metabolic pathways. Key genes, including GALNT6, were validated through quantitative real-time PCR. The effects of GALNT6 knockdown on lenvatinib sensitivity were examined in vitro and in vivo. O-GalNAc glycosylation was assessed using Vicia Villosa Lectin. Immune cell infiltration and interactions were analyzed in the TCGA-LIHC cohort, with further validation by Western blotting and immunohistochemistry.

resultsOur findings indicate that lenvatinib resistance in HCC is driven by the mucin-type O-glycosylation pathway, with GALNT6 playing a critical role. Knockdown of GALNT6 led to reduced O-GalNAc glycosylation, including the modification of LAPTM5, resulting in decreased LAPTM5 activity and autophagy inhibition. Additionally, GALNT6 silencing disrupted the PDGFA-PDGFRB axis, impairing the activation of cancer-associated fibroblasts (CAFs) and reducing their secretion of SPP1, which collectively diminished lenvatinib resistance.

conclusionsGALNT6 is integral to the resistance mechanisms against lenvatinib in HCC by modulating autophagy and CAF activation. Targeting GALNT6 offers a promising strategy to enhance lenvatinib efficacy and improve therapeutic outcomes in HCC.

Indexed as

AutophagyCancer-Associated FibroblastsCarcinoma, HepatocellularDrug Resistance, NeoplasmLiver NeoplasmsN-AcetylgalactosaminyltransferasesPhenylurea CompoundsPolypeptide N-acetylgalactosaminyltransferaseQuinolinesAnimalsAntineoplastic AgentsCell Line, TumorGlycosylationHumansMiceMice, NudeAntineoplastic AgentslenvatinibN-AcetylgalactosaminyltransferasesPhenylurea CompoundsPolypeptide N-acetylgalactosaminyltransferaseQuinolinesCAFsGALNT6LAPTM5Lenvatinib resistanceMucin-type O-glycosylation

Identifiers

PMID39718738
PMCPMC12974011

What OpenQuestion holds

Textmetadata
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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.