YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer

Sardo, Federica Lo; Pulito, Claudio; Sacconi, Andrea; Korita, Etleva; Sudol, Marius; Strano, Sabrina; Blandino, Giovanni

doi:10.1016/j.canlet.2020.11.037

Cited by 60 publications

(38 citation statements)

References 46 publications

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“…With the concomitant transcriptional activity in favor of the expression of pro-survival genes, YAP is able also to mediate genetic repression of several tumor suppressor genes. This topic has been reported very recently in two seminal papers by Hoxha et al [ 119 ] and Lo Sardo et al [ 120 ]. The first describes how a molecular complex composed by the association of YAP with the factor Yin Yang 1 (YY1), Polycomb repressive complex (PRC2) and the trimethylation of Histone H3 protein (which means genetic silencing) can inhibit CDKN1B gene [ 119 ].…”

Section: Yap-dependent Signaling Pathways Impacting Cancermentioning

confidence: 79%

“…The second one demonstrated once again how the TGF-β pathway and YAP signaling are interconnected. Indeed, YAP expression induces a significant downregulation of TGF-β Receptor 2 (TGFBR2) through the orchestrated action of miR-106b-25, post-transcriptionally, and with the help of Enhancer Of Zeste 2 (EZH2, the functional active part of PRC2), a new YAP target involved in the triple methylation of Histone H3 [ 120 ]. EZH2 would act as mediator, without any kind of heterodimerization with YAP, but the depletion of both proteins reduces colony formation and tumor growth [ 120 ].…”

Section: Yap-dependent Signaling Pathways Impacting Cancermentioning

confidence: 99%

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An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

Morciano

Vezzani

Missiroli

et al. 2021

Cancers

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Yes-associated protein (YAP) has emerged as a key component in cancer signaling and is considered a potent oncogene. As such, nuclear YAP participates in complex and only partially understood molecular cascades that are responsible for the oncogenic response by regulating multiple processes, including cell transformation, tumor growth, migration, and metastasis, and by acting as an important mediator of immune and cancer cell interactions. YAP is finely regulated at multiple levels, and its localization in cells in terms of cytoplasm–nucleus shuttling (and vice versa) sheds light on interesting novel anticancer treatment opportunities and putative unconventional functions of the protein when retained in the cytosol. This review aims to summarize and present the state of the art knowledge about the role of YAP in cancer signaling, first focusing on how YAP differs from WW domain-containing transcription regulator 1 (WWTR1, also named as TAZ) and which upstream factors regulate it; then, this review focuses on the role of YAP in different cancer stages and in the crosstalk between immune and cancer cells as well as growing translational strategies derived from its inhibitory and synergistic effects with existing chemo-, immuno- and radiotherapies.

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Section: Yap-dependent Signaling Pathways Impacting Cancermentioning

confidence: 79%

Section: Yap-dependent Signaling Pathways Impacting Cancermentioning

confidence: 99%

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

Morciano

Vezzani

Missiroli

et al. 2021

Cancers

View full text Add to dashboard Cite

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“…In our study, we first identified differentially expressed kinases that interacted with CEMIP in BC and performed enrichment analysis on these genes, including CEMIP . We noted that DDR2 , PTK2 , RET , TGFBR2 , PRKD2 , and CEMIP were involved in positive regulation of cell migration, indicating that CEMIP might participate in cancer cell migration by interacting with these genes, of which DDR2 and TGFBR2 were down-regulated in BC and proved to inhibit cancer metastasis ( Lo Sardo et al, 2021 ; Mehta et al, 2021 ), while PTK2 , RET , and PRKD2 were up-regulated in BC and were shown to promote cancer development ( Azoitei et al, 2014 ; Fan et al, 2019 ; Subbiah and Cote, 2020 ). However, no studies have revealed the relationships between them yet.…”

Section: Discussionmentioning

confidence: 99%

High Expression of CEMIP Correlates Poor Prognosis and the Tumur Microenvironment in Breast Cancer as a Promisingly Prognostic Biomarker

et al. 2021

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Cell migration-inducing hyaluronidase 1 (CEMIP), a Wnt-related protein and also known as KIAA1199, is implicated in the process of metastatic colonization in a variety of malignant tumors, including breast cancer (BC), which is one of the most frequently diagnosed tumors in women worldwide. In this study, multiple public databases, online analytical tools, and bioinformatics approaches were applied to explore the expression levels, regulatory mechanisms, and biological functions of CEMIP in BC. We illustrated that CEMIP was highly expressed in various kinds of carcinomas, including BC, especially advanced subtypes, and predicted less favorable prognosis (negatively associated with overall survival) in BC patients, which might be an independent prognostic factor. Then, we revealed that the mutation and high expression of CEMIP might lead to it as an oncogene. We also demonstrated that TP53 mutation, DNA hypo-methylation, and the expression changes of three potential upstream transcription factors (EZH2, EGR1, and JUN) of CEMIP were likely to cause the hyperexpression of CEMIP in BC. Moreover, our findings suggested that CEMIP might exert its carcinogenic roles in the tumor microenvironment via participation in the extracellular matrix formation, increasing cancer-associated fibroblast (CAF), M2 macrophage, and neutrophil infiltration and decreasing CD8+ T cell infiltration. In summary, our study provided more solid evidence for CEMIP as a prognostic and metastatic biomarker and a potential therapeutic target in BC. Of course, these findings also need more confirmations of basic experiments and further clinical trials in the future.

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“…In addition, TGFBR2 binds with ligand and interacts with TGFBR1 to construct a hetero-tetrameric complex, activating smad2 and smad3 to interact with smad4. Eventually, the smad members translocate into nucleus to associate with transcription factors to regulate target gene expression [ 30 ]. Moreover, TGF-β signals exist crosstalk with AKT signaling pathway, thereby activated TGF-β could exert promoting function of cancer.…”

Section: Discussionmentioning

confidence: 99%

CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

Chen

Liu

et al. 2021

Cancer Cell Int

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Background Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear. Methods Real-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies. Results The expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer. Conclusions These findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.

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YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer

Cited by 60 publications

References 46 publications

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

High Expression of CEMIP Correlates Poor Prognosis and the Tumur Microenvironment in Breast Cancer as a Promisingly Prognostic Biomarker

CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

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