Evidence map›Paper›PMID 31337986›Full record

ArticleCancer cell international2019

YAP promotes multi-drug resistance and inhibits autophagy-related cell death in hepatocellular carcinoma via the RAC1-ROS-mTOR pathway.

Yuan Zhou, Yubo Wang, Wuhua Zhou, Tianchi Chen, Qinchuan Wu, Vikram Kumar Chutturghoon, Bingyi Lin, Lei Geng, Zhe Yang, Lin Zhou and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% of its field
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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

  1. Pooled it
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  17. YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  18. Article
  19. Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023
    Review
  20. Article

13 more citing papers are in PubMed but not listed here.

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

11 authors at 1 institution in 1 country.

Yuan Zhou *1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yubo Wang *1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Wuhua Zhou1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Tianchi Chen1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Qinchuan Wu1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Vikram Kumar Chutturghoon1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Bingyi Lin1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Lei Geng1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Zhe Yang1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Lin Zhou1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Shusen Zheng1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Zhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMulti-drug resistance is the major cause of chemotherapy failure in hepatocellular carcinoma (HCC). YAP, a critical effector of the Hippo pathway, has been shown to contribute to the progression, metastasis and invasion of cancers. However, the potential role of YAP in mediating drug resistance remains obscure.

methodsRT-qPCR and western blot were used to assess YAP expression in HCC cell lines. CCK-8 assays, flow cytometry, a xenograft tumour model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on multi-drug resistance, intracellular ROS production and the autophagy of HCC cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP promotes chemoresistance in HCC cells.

resultsWe found that BEL/FU, a typical HCC cell line with chemoresistance, exhibited overexpression of YAP. Moreover, the inhibition of YAP by shRNA or verteporfin conferred the sensitivity of BEL/FU cells to chemotherapeutic agents through autophagy-related cell death in vitro and in vivo. Mechanistically, YAP silencing significantly enhanced autophagic flux by increasing RAC1-driven ROS, which contributed to the inactivation of mTOR in HCC cells. In addition, the antagonist of autophagy reversed the enhanced effect of YAP silencing on cell death under treatment with chemotherapeutic agents.

conclusionOur findings suggested that YAP upregulation endowed HCC cells with multi-drug resistance via the RAC1-ROS-mTOR pathway, resulting in the repression of autophagy-related cell death. The blockade of YAP may serve as a promising novel therapeutic strategy for overcoming chemoresistance in HCC.

Indexed as

Autophagy-related cell deathHepatocellular carcinomaMulti-drug resistanceYes-associated protein (YAP)

Identifiers

PMID31337986
PMCPMC6626386
OpenAlexW2960036894

What OpenQuestion holds

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LicenceCC BY
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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.