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Title: YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer
Authors: Lo Sardo, Federica
Pulito, Claudio
Sacconi, Andrea
Korita, Etleva
Sudol, Marius 
Strano, Sabrina
Blandino, Giovanni
Keywords: Dasatinib
Hippo pathway
Lung cancer
Issue Date: 1-Mar-2021
Publisher: Elsevier Ireland Ltd
Citation: Lo Sardo, Federica, Pulito, Claudio, Sacconi, Andrea, Korita, Etleva, Sudol, Marius, Strano, Sabrina, Blandino, Giovanni (2021-03-01). YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer. Cancer Letters 500 : 51-63. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: Lung cancer is the leading cause of cancer-related deaths, worldwide. Non–small cell lung cancer (NSCLC) is the most prevalent lung cancer subtype. YAP and TAZ have been implicated in lung cancer by acting as transcriptional co-activators of oncogenes or as transcriptional co-repressors of tumor suppressor genes. Previously we reported that YAP and TAZ regulate microRNAs expression in NSCLC. Among the set of regulated miRNAs, the oncogenic miR-25, 93, and 106b, clustering within the MCM7 gene were selected for further studies. We firstly identified Transforming Growth Factor-? (TGF-?) Receptor 2 (TGFBR2), a member of the TGF-? signaling, as a target of the miRNA cluster, which exhibited prognostic value because of its tumor suppressor activity. We found that YAP/TAZ-mediated repression of TGFBR2 occurs both: post-transcriptionally through the miR-106b-25 cluster and transcriptionally by engaging the EZH2 epigenetic repressor that we reported here as a novel target gene of YAP/TAZ. Furthermore, we document that YAP/TAZ and EZH2 cooperate in lung tumorigenesis by transcriptionally repressing a specific subset of tumor suppressor genes, including TGFBR2. Our findings point to YAP/TAZ and EZH2 as potential therapeutic targets for NSCLC treatment. © 2020 The Authors
Source Title: Cancer Letters
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2020.11.037
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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