YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33413409", "kind": "science-record", "revision": 7, "content_hash": "sha256:b3012ee8876a390847beaf7cc7b28c2d73e8d3a487656aa040ac24907aa1a43d", "created_at": "2026-11-01T15:41:22Z", "updated_at": "2026-11-01T22:02:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas.", "doi": "10.1186/s12935-020-01688-9", "pmid": "33413409", "authors": ["Wei Xu", "Mingjiong Zhang", "Yue Li", "Yu Wang", "Kai Wang", "Qiaoyu Chen", "Runjie Zhang", "Weiwei Song", "Qiqing Huang", "Weihong Zhao", "Jianqing Wu"], "journal": "Cancer cell international", "year": 2021, "abstract": "BACKGROUND: Autophagy is a double-edged sword during the initiation and progression of multiple tumors. The Hippo pathway effector YAP has been proved to be involved in autophagy processes. The present study aimed to investigate how YAP regulates cell proliferation via autophagy in lung adenocarcinomas (LUAD).\nMETHODS: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YAP expression in LUAD cell lines. CCK-8 assay, 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 treatment and rescue experiments were carried out to elucidate the mechanism by which YAP manipulates autophagy in LUAD cells.\nRESULTS: YAP was significantly overexpressed in samples of LUAD patients and its expression level is related to 5-year survival. YAP manipulated the proliferation and autophagy in A549 and H1299 LUAD cells. YAP could induce 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.\nCONCLUSIONS: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.", "claims": [{"id": "claim-method", "statement": "Independent samples t-test performed for GSE43458 data, the result showed that YAP mRNA expression of LUAD tissues was significantly higher than that of normal lung tissues (P = 0.028, Fig. 1a).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33413409", "locator": "sections[13] \"YAP is upregulated in LUAD tissues and is associated with poor prognosis of 5-year survival\" paragraph 2", "quote": "Independent samples t-test performed for GSE43458 data, the result showed that YAP mRNA expression of LUAD tissues was significantly higher than that of normal lung tissues (P = 0.028, Fig. 1a)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Not applicable.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33413409", "locator": "sections[21] \"Acknowledgements\" paragraph 2", "quote": "Not applicable."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33413409"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE43458"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE43458"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33413409", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-020-01688-9", "sha256": 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"licence_read": false}}, {"id": "asset:table:pmid:33413409:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b2b14bc110505b86be6b639643994093b68d929f8c8b3719a4844960b9880de3", "bytes": 678, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab1", "version": null, "note": "The character of YAP expression among the different groups in lung adenocarcinoma patients at The Cancer Genome Atlas (TCGA) database", "structure": {"pmcid": "PMC7791871", "section_index": 13, "section_title": "YAP is upregulated in LUAD tissues and is associated with poor prognosis of 5-year survival", "row_count": 10, "column_count": 4}, "table": {"label": "Table 1", "caption": "The character of YAP expression among the different groups in lung adenocarcinoma patients at The Cancer Genome Atlas (TCGA) database", "rows": [["Description", "Number", "Mean (95% 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RT-qPCR and Western blot were performed to assess YA", "ained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YA"], "order_basis": "paper_text_order:444", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["m Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YAP expression in L"], "order_basis": "paper_text_order:456", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["to assess YAP expression in LUAD cell lines. CCK-8 assay, xenograft tumor model, immunochemistr"], "order_basis": "paper_text_order:529", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor treatment and rescue ex", "and promoted the proliferation in vitro and in vivo. CONCLUSIONS: Hippo pathway critical transcr"], "order_basis": "paper_text_order:699", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nipulated the proliferation and autophagy in A549 and H1299 LUAD cells. YAP could induce activ", "(Shanghai, China). A549 and H1299 cells were cultured in RPMI1640 medium (Gibco, USA) containing 10%", "s Cell culture and reagents Human LUAD cells A549 and H1299 were purchased from the Chinese Ac", "inese Academy of Sciences (Shanghai, China). A549 and H1299 cells were cultured in RPMI1640 me"], "order_basis": "paper_text_order:1034", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["analysis of variance"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}