Evidence map›Paper›PMID 40467995›Full record

ArticleNature cancer2025

RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma.

Fanzheng Meng, Hairui Li, Yabin Huang, Chunxu Wang, Yufeng Liu, Chunting Zhang, Danlei Chen, Taofei Zeng, Shenyu Zhang, Yunyun Li and 13 more

Erratum issuedAbstract read
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In one paragraph

Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Review
  2. Aberrant phase separation from a rare ABI3 mutation drives microglial dysfunction and Alzheimer's risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Pharmacological modulation of stress granulesFrontiers in pharmacology · 2026
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Emerging roles of stress granules in liver diseases: a comprehensive review.Frontiers in cell and developmental biology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Fanzheng Meng *Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Hairui Li *Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Yabin Huang *Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Chunxu Wang *Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Yufeng Liu *Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Chunting ZhangDepartment of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Danlei ChenDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Taofei ZengDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Shenyu ZhangDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Yunyun LiDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Bo ZhangDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Chuandong LangDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Jie XiaDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Wanxiang XiongDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Shixiang PanDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Xuedan SunDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Rick F ThorneTranslational Research Institute, Henan Provincial People's Hospital, Zhengzhou, China.
Yao LiuDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.ORCID http://orcid.org/0000-0003-0365-3229
Jiabei WangDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. jbwang16@ustc.edu.cn.ORCID http://orcid.org/0000-0002-4578-3817
Shugeng ZhangDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. shugeng517@163.com.ORCID http://orcid.org/0000-0001-9832-9784
Ruipeng SongDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. songruipeng@ustc.edu.cn.ORCID http://orcid.org/0000-0002-1912-3735
Jizhou WangDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. wangjizhou1984@hotmail.com.ORCID http://orcid.org/0000-0002-6934-072X
Lianxin LiuDepartment of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. liulx@ustc.edu.cn.ORCID http://orcid.org/0000-0002-3535-6467

Funding

Anhui Department of Education (Department of Education of Anhui Province) 2022AH020077Chinese Society of Clinical Oncology (Chinese Society of Clinical Oncology, Beijing Xisike Clinical Oncology Research Foundation) Y-JS2019-014National Natural Science Foundation of China (National Science Foundation of China) 82101480National Natural Science Foundation of China (National Science Foundation of China) 82103219National Natural Science Foundation of China (National Science Foundation of China) 82170618National Natural Science Foundation of China (National Science Foundation of China) 82272700National Natural Science Foundation of China (National Science Foundation of China) 82272787National Natural Science Foundation of China (National Science Foundation of China) U19A2008、81972307Natural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation) 2108085MH288Natural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation) 2108085QH325Natural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation) 2108085QH343Natural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation) 2208085J47Natural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation) 2208085MH245Postdoctoral Research Foundation of China (China Postdoctoral Research Foundation) 2021TQ0324Postdoctoral Research Foundation of China (China Postdoctoral Research Foundation) 2022T150623,2020M682023University of Science and Technology of China (USTC) WK9110000153University of Science and Technology of China (USTC) WK9110000164University of Science and Technology of China (USTC) YD9100002003University of Science and Technology of China (USTC) YD9110002048
6 · The paper itself

Abstract

Resistance to tyrosine kinase inhibitors (TKIs) dampens their clinical efficacy in hepatocellular carcinoma (HCC). Stress granules formed by phase separation are essential to stress response and can be involved in therapy resistance, but their mechanisms in HCC are unclear. Here our screen shows that the atypical serine/threonine kinase RIOK1 is highly expressed in HCC, linked to poor prognosis, and transcriptionally activated by NRF2 under various stress conditions. RIOK1 undergoes liquid-liquid phase separation by incorporating IGF2BP1 and G3BP1 into stress granules that sequestrate PTEN messenger RNA reducing its translation. This process activates the pentose phosphate pathway, facilitating stress resolution and cytoprotection against TKI. We further show that the small-molecule inhibitor chidamide downregulates RIOK1 and enhances TKI efficacy. RIOK1-positive stress granules are found in donafenib-resistant tumors from patients with HCC. These findings reveal a link between stress granule dynamics, metabolic reprogramming and HCC progression, offering the potential means to improve TKI efficacy.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsProtein Serine-Threonine KinasesPTEN PhosphohydrolaseStress GranulesAnimalsBenzamidesBenzylaminesCell Line, TumorCell ProliferationDNA HelicasesDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansMiceNF-E2-Related Factor 2BenzamidesBenzylaminesDNA HelicasesG3BP1 protein, humanNFE2L2 protein, humanNF-E2-Related Factor 2Poly-ADP-Ribose Binding ProteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesPTEN PhosphohydrolasePTEN protein, humanRNA-Binding ProteinsRNA HelicasesRNA Recognition Motif Proteins

Identifiers

PMID40467995

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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.