Evidence map›Paper›PMID 37215986›Full record

ArticleInternational journal of biological sciences2023

YAP1 synergize with YY1 transcriptional co-repress DUSP1 to induce osimertinib resistant by activating the EGFR/MAPK pathway and abrogating autophagy in non-small cell lung cancer.

Yue Ning, Hongmei Zheng, Yang Yang, Hongjing Zang, Weiyuan Wang, Yuting Zhan, Haihua Wang, Jiadi Luo, Qiuyuan Wen, Jinwu Peng and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

26 citing papers in PubMed, 25 citations in OpenAlex.

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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 at 3 institutions in 1 country.

Yue NingDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hongmei ZhengDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yang YangDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hongjing ZangDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Weiyuan WangDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yuting ZhanDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Haihua WangDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jiadi LuoDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Qiuyuan WenDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jinwu PengDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Juanjuan XiangCancer Research Institute, Central South University, Changsha, Hunan, China.
Songqing FanDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Second Xiangya Hospital of Central South University · CNCentral South University · CNXiangya Hospital Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

YAP1 is a well-known core effector of the Hippo pathway in tumors, but its potential role in osimertinib resistance remained unexplored. Our study provides evidence that YAP1 acts as a potent promoter of osimertinib resistance. By inhibiting YAP1 with a novel inhibitor, CA3, and combining it with osimertinib, we observed a significant suppression of cell proliferation and metastasis, induction of apoptosis and autophagy, and a delay in the emergence of osimertinib resistance. Interestingly, CA3 combined with osimertinib executed its anti-metastasis and pro-tumor apoptosis in part through autophagy. Mechanistically, we found that YAP1, in collaboration with YY1, transcriptionally represses DUSP1, leading to the dephosphorylation of the EGFR/MEK/ERK pathway and YAP1 phosphorylation in osimertinib-resistant cells. Our results also validate that CA3, in combination with osimertinib, executes its anti-metastasis and pro-tumor apoptosis partly through autophagy and the YAP1/DUSP1/EGFR/MEK/ERK regulatory feedback loop in osimertinib-resistant cells. Remarkably, our findings illustrate that YAP1 protein is upregulated in patients after osimertinib treatment and osimertinib resistance. Overall, our study confirms that the YAP1 inhibitor CA3 increases DUSP1 with concomitant activation of the EGFR/MAPK pathway and induces autophagy to enhance the efficacy of third-generation EGFR-TKI treatments for NSCLC patients.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAcrylamidesAniline CompoundsAutophagyCell Line, TumorDrug Resistance, NeoplasmDual Specificity Phosphatase 1ErbB ReceptorsHumansIndolesMitogen-Activated Protein Kinase KinasesMutationPyrimidinesYY1 Transcription FactorAcrylamidesAniline CompoundsDual Specificity Phosphatase 1DUSP1 protein, humanEGFR protein, humanErbB ReceptorsIndolesMitogen-Activated Protein Kinase KinasesosimertinibPyrimidinesYY1 protein, humanYY1 Transcription FactorAutophagyEGFR-TKIHippo pathwayOsimertinibYAP1

Identifiers

PMID37215986
PMCPMC10197898
OpenAlexW4377565045

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.