Evidence map›Paper›PMID 41776050›Full record

ArticleOncogene2026

Ginkgetin targets GRP78 to induce dual pathways of ER stress and immune activation in osteosarcoma.

Wenyuan Xu, Tongtong Liu, Xinglong Ma, He Dong, Yinghao Cao, Guanyi Li, Zhuoying Wang, Yingqi Hua, Zhengdong Cai, Mengxiong Sun and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Wenyuan Xu *Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tongtong Liu *Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xinglong MaDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
He DongDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0009-0005-6102-8204
Yinghao CaoDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Guanyi LiSchool of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.ORCID http://orcid.org/0009-0008-5434-1923
Zhuoying WangDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yingqi HuaDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-7277-0958
Zhengdong CaiDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mengxiong SunDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. sunmengxiong@126.com.ORCID http://orcid.org/0000-0002-5514-7160
Jingjie LiPrecision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jingjieli@sjtu.edu.cn.
Tao ZhangDepartment of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhangtaoabc2008@sjtu.edu.cn.ORCID http://orcid.org/0000-0002-5578-9913

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma is an aggressive malignancy characterized by rapid proliferation and a propensity for metastasis. The endoplasmic reticulum (ER) chaperone GRP78, a critical regulator of osteosarcoma progression, represents a promising therapeutic target. In this study, we identified the natural compound ginkgetin (Gink) as a novel GRP78 inhibitor. Cellular thermal shift assays, surface plasmon resonance, and mutagenesis studies revealed that Gink directly binds to GRP78, with K296 serving as a key interaction site. In vitro, Gink suppressed osteosarcoma cell proliferation, migration, and invasion while inducing apoptosis and autophagy by activating the PERK-eIF2α-ATF4 pathway. Co-immunoprecipitation assays showed that Gink competitively disrupted GRP78-PERK interaction. In orthotopic and patient-derived xenograft models, Gink treatment markedly attenuated tumor growth and metastasis. Gink also reprogrammed the tumor immune microenvironment by reducing M2 macrophage polarization and synergizing with anti-PD1 therapy to enhance CD8

Indexed as

Bone NeoplasmsEndoplasmic Reticulum StressHeat-Shock ProteinsOsteosarcomaAnimalsApoptosisAutophagyBiflavonoidsCell Line, TumorCell ProliferationeIF-2 KinaseEndoplasmic Reticulum Chaperone BiPHumansIntegrated Stress ResponseMiceSignal TransductionBiflavonoidseIF-2 KinaseEndoplasmic Reticulum Chaperone BiPginkgetinHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mouse

Identifiers

PMID41776050

What OpenQuestion holds

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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.