YAP1 is essential for tumor growth and is a potential therapeutic target for EGFR-dependent lung adenocarcinomas

Lee, Ting-Fang; Tseng, Yu-Chi; Chang, Wei‐Jen; Chen, Yi‐Chen; Kao, Yu-Rung; Chou, Teh-Ying; Ho, Chao‐Chi; Wu, Cheng‐Wen

doi:10.18632/oncotarget.19647

Cited by 18 publications

(15 citation statements)

References 50 publications

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“…In NSCLC patients, TEAD activity correlates with the EGFR mutation status. EGFR mutant lung cancer tissues and cell lines show upregulated YAP expression, followed by increased TEAD activity [165]. Although EGFR acquires drug resistance to TKI via the T790M mutation, TEAD inhibition effectively reduces the viability of TKI-resistant lung adenocarcinoma cells [166,167].…”

Section: Teads As Mediators Of Cancer Genesmentioning

confidence: 99%

Regulation of TEAD Transcription Factors in Cancer Biology

Huh

Kim

Jeong

et al. 2019

Cells

200

157

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Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

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Section: Teads As Mediators Of Cancer Genesmentioning

confidence: 99%

Regulation of TEAD Transcription Factors in Cancer Biology

Huh

Kim

Jeong

et al. 2019

Cells

200

157

View full text Add to dashboard Cite

show abstract

“…Likewise, Epidermal Growth Factor Receptor (EGFR) signaling, which is altered in many cancers, regulates YAP/TAZ activity. EGFR-mediated regulation of the Hippo pathway was first described in Drosophila [ 336 ], and subsequent studies showed that EGFR activation inhibits the Hippo pathway to promote YAP/TAZ activity [ 337 , 338 , 339 ]. Importantly, EGFR-mediated YAP/TAZ activity can drive cancer development and progression [ 105 , 338 , 339 , 340 , 341 ].…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

“…EGFR-mediated regulation of the Hippo pathway was first described in Drosophila [ 336 ], and subsequent studies showed that EGFR activation inhibits the Hippo pathway to promote YAP/TAZ activity [ 337 , 338 , 339 ]. Importantly, EGFR-mediated YAP/TAZ activity can drive cancer development and progression [ 105 , 338 , 339 , 340 , 341 ]. In addition, studies also show that YAP/TAZ activation is a mechanism of resistance to EGFR inhibitors [ 97 , 342 , 343 , 344 , 345 ].…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

Warren

Xiao

2018

Cancers

142

131

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Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) have both emerged as important drivers of cancer progression and metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive human cancers. There is abundant experimental evidence demonstrating that YAP or TAZ activation promotes cancer formation, tumor progression, and metastasis. In this review we summarize the evidence linking YAP/TAZ activation to metastasis, and discuss the roles of YAP and TAZ during each step of the metastatic cascade. Collectively, this evidence strongly suggests that inappropriate YAP or TAZ activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ activation is a promising strategy for the treatment of metastatic disease. To this end, we also discuss several potential strategies for inhibiting YAP/TAZ activation in cancer and the challenges each strategy poses.

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“…Therefore, the combination of YAP1 knockdown and administration of sorafenib could exert a stronger inhibitory effect on tumor progression compared with YAP1 knockdown or sorafenib alone. 38 , 39 …”

Section: Discussionmentioning

confidence: 99%

<p>Targeting Yes1 Associated Transcriptional Regulator Inhibits Hepatocellular Carcinoma Progression and Improves Sensitivity to Sorafenib: An in vitro and in vivo Study</p>

Guo¹,

Zheng²,

Luo³

et al. 2020

OTT

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Purpose The aim of this study was to investigate the role of Yes1 associated transcriptional regulator (YAP1) in the pathology of hepatocellular carcinoma (HCC) and its potential as a therapeutic target. Methods YAP1 expression in HCC and adjacent tissues was determined via immunohistochemistry; in HCC and human normal liver cell lines, expression was examined via Western blotting. The effects of YAP1 knockdown and overexpression were detected following transfection of HCC cells with siRNA-YAP1 recombinants or pcDNA3.1-YAP1 plasmids. A tumor xenograft model was constructed by implanting YAP1-knockdown lentivirus-infected Hep-3B cells into nude mice, and the animals were treated with sorafenib. Results In patients with HCC, YAP1 was upregulated in tumor tissue compared with adjacent tissue, and its high expression in the tumor was associated with increased Edmonson grade. In vitro, YAP1 expression was increased in Hep-3B, SK-HEP-1 and Huh7 cells, while it was similar in SMMC-7721 cells and LO2 cells. Meanwhile, YAP1 increased cell proliferation and invasion, promoted the progression of epithelial–mesenchymal transition, and inhibited cell apoptosis in HCC cells; furthermore, YAP1 knockdown combined with the administration of sorafenib decreased cell viability and increased cell apoptosis compared with YAP1 knockdown or treatment with sorafenib alone. In vivo, YAP1 knockdown inhibited tumor growth and metastasis, whereas it promoted apoptosis; meanwhile, YAP1 knockdown synergized with sorafenib to suppress tumor progression in HCC mice. Conclusion YAP1 is upregulated in both HCC tumor tissues and cell lines. Moreover, it promotes cell proliferation and invasion and promoted the progression of epithelial–mesenchymal transition in vitro. Furthermore, targeting YAP1 inhibits HCC progression and improves sensitivity to sorafenib in vitro and in vivo.

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YAP1 is essential for tumor growth and is a potential therapeutic target for EGFR-dependent lung adenocarcinomas

Cited by 18 publications

References 50 publications

Regulation of TEAD Transcription Factors in Cancer Biology

Regulation of TEAD Transcription Factors in Cancer Biology

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

<p>Targeting Yes1 Associated Transcriptional Regulator Inhibits Hepatocellular Carcinoma Progression and Improves Sensitivity to Sorafenib: An in vitro and in vivo Study</p>

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