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YAP Manipulates Proliferation Via PTEN/AKT/mTOR-mediated Autophagy in Lung Adenocarcinomas
Jianqing Wu
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0030-201X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Cancer Cell International.
Background: Autophagy is a double-edged sword during the initiation or progression of multiple tumors. Hippo pathway core-factor YAP has been proved to be involved in autophagy processes. The present study aimed to identify the mechanism underlying modulation of YAP via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas (LUAD).
Methods: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were used to assess YAP expression in LUAD cell lines. CCK-8 assay, flow cytometry, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP manipulating autophagy in LUAD cells.
Results: YAP significantly overexpressed in samples of LUAD patients and related to 5-year survival. YAP manipulates the proliferation and autophagy of A549 and H1299 LUAD cells. YAP induces activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo.
Conclusions: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.
Keywords
LUADs, YAP, PTEN/AKT/mTOR, Autophagy
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CURRENT STATUS: Published
Version 1
Posted 22 Sep, 2020
Published
On 07 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 12 Oct, 2020
Review #2 received
Received 12 Oct, 2020
Review #1 received
Received 09 Oct, 2020
Reviewers invited
Invitations sent on 24 Sep, 2020
Reviewer #1 agreed
On 24 Sep, 2020
Reviewer #2 agreed
On 24 Sep, 2020
Editor assigned
On 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
First submitted
On 15 Sep, 2020
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Subject Areas
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This preprint is under consideration at Cancer Cell International. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
YAP Manipulates Proliferation Via PTEN/AKT/mTOR-mediated Autophagy in Lung Adenocarcinomas
Jianqing Wu
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0030-201X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 1
Posted 22 Sep, 2020
Published
On 07 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 12 Oct, 2020
Review #2 received
Received 12 Oct, 2020
Review #1 received
Received 09 Oct, 2020
Reviewers invited
Invitations sent on 24 Sep, 2020
Reviewer #1 agreed
On 24 Sep, 2020
Reviewer #2 agreed
On 24 Sep, 2020
Editor assigned
On 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
First submitted
On 15 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Cancer Cell International.
Background: Autophagy is a double-edged sword during the initiation or progression of multiple tumors. Hippo pathway core-factor YAP has been proved to be involved in autophagy processes. The present study aimed to identify the mechanism underlying modulation of YAP via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas (LUAD).
Methods: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were used to assess YAP expression in LUAD cell lines. CCK-8 assay, flow cytometry, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP manipulating autophagy in LUAD cells.
Results: YAP significantly overexpressed in samples of LUAD patients and related to 5-year survival. YAP manipulates the proliferation and autophagy of A549 and H1299 LUAD cells. YAP induces activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo.
Conclusions: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.