An overview of signaling pathways regulating YAP/TAZ activity

Heng, Boon Chin; Zhang, Xuehui; Aubel, Dominique; Bai, Yunyang; Li, Xiaochan; Yan, Wei; Fussenegger, Martin; Deng, Xuliang

doi:10.1007/s00018-020-03579-8

Cited by 83 publications

(68 citation statements)

References 128 publications

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“…The present study identified that upregulation of circ-CCT3 facilitated HCC cell progression by sponging miR-1287-5p to regulate TEA domain transcription factor 1 (TEAD1) expression. TEAD1 transcriptional activity is widely believed to be modulated by the presence or absence of nuclear Yes-associated protein (YAP)/transcriptional activator with PDZ-binding domain (TAZ) (10). The present study found that TEAD1 could directly activate patched 1 (PTCH1) and lysyl oxidase (LOX) transcription.…”

Section: Introductionmentioning

confidence: 64%

Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis

et al. 2021

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Hepatocellular carcinoma (HCC) is characterized by a poor prognosis because of its insensitivity to radiation and chemotherapy. Recently, circular RNAs (circRNAs) have been found to serve important roles in hepatocellular carcinogenesis. circ-CCT3, a novel circRNA, was screened from the differential tissue expression results of a circRNA microarray. Relative expression levels of circ-CCT3 in specimens and cell lines were evaluated by reverse transcription-quantitative PCR and the relationship between circ-CCT3 and prognosis was analyzed by Kaplan-Meier curves. The oncogenic role of circ-CCT3 was confirmed in HCC cells through a cell counting kit-8 (CCK-8) assay, a colony formation assay, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, a wound-healing assay and a Transwell assay. Bioinformatics prediction and luciferase reporter assays validated that circ-CCT3 facilitated HCC progression through the miR-1287-5p/TEA domain transcription factor 1 (TEAD1) axis. TEAD1 could then directly activate patched 1 and lysyl oxidase transcription, as analyzed by chromatin immunoprecipitation and luciferase reporter assays. The present study identified a novel circRNA, circ-CCT3, which may be used as a potential therapeutic target for HCC.

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Section: Introductionmentioning

confidence: 64%

Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis

et al. 2021

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“…KIF4A spinning cone in the late adjustment form and plays a key role in the process of mitosis; the anomaly can lead to abnormal mitosis checkpoint and DNA damage repair, and chromosome instability and the formation of aneuploidy, cause abnormal cell proliferation, differentiation and cause tumor formation 8,9 . Some scholars have found that intracellular KIF4A can lead to mitotic defects, such as high chromosome concentration and chromosome aneuploidy, while the Hippo signaling pathway plays a key role in limiting the transformation of chromosomes from biploid to polyploid/aneuploid 10,11 . Previous studies have shown that inactivation of LATS1/2, a key kinase in the Hippo signaling pathway, or overexpression of YAP, a target gene downstream of the Hippo signaling pathway, can lead to substantial accumulation of E3 ubiquitin ligase Skp2 in the cytoplasm and decrease of Skp2 level in the nucleus, leading to cell mitosis arrest and polyploid formation 12,13 .…”

Section: Introductionmentioning

confidence: 99%

KIF4A enhanced cell proliferation and migration via Hippo signaling and predicted a poor prognosis in esophageal squamous cell carcinoma

et al. 2020

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Background In this study, we aimed to explore and clarify the function of KIF4A in esophageal squamous cell carcinoma (ESCC). Methods The microarray data were extracted from the Gene Expression Omnibus (GEO) database. We then used the database for Annotation, Visualization, and Integrated Discovery (DAVID) to perform the gene ontology function (GO) and KEGG Orthology‐Based Annotation System (KOBAS) to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs). The six core candidate genes were identified using protein–protein interaction (PPI) network analysis and Cytoscape software. Among them, the expression of KIF4A were validated by UALCAN database from the Cancer Genome Atlas (TCGA) (P < 0.05). Western blotting, qRT‐PCR and IHC were used to detect the expression of KIF4A in tissues. Cell experiments (transwell migration assays, wound healing assay, CCK8 assay, and clone formation experiment) were utilized to verify the roles of KIF4A on the ESCC cells. Western blotting was used to explore the mechanism of KIF4A in ESCC. Results The expression level of KIF4A was upregulated in ESCC samples compared to those in paracancerous tissues. Transwell migration and wound healing assay showed overexpression of KIF4A significantly promoted the migration of ESCC cells. CCK8 assay and clone formation experiment analysis showed that overexpression of KIF4A promoted proliferation of ESCC cells. Western blot detection found that KIF4A could affect the phosphorylation level of Hippo signaling pathway related proteins. Conclusions In summary, KIF4A promotes ESCC cell proliferation and migration by regulating the biological function of ESCC cells through the Hippo signaling pathway. Key points Significant findings of the study We found that high KIF4A expression was associated with poor overall survival in esophageal squamous cell carcinoma. KIF4A expression also promoted the proliferation and migration of ESCC cells in vitro. What this study adds Our experimental results explain the role of KIF4A in ESCC, and provide a new biomolecular target for the treatment of ESCC.

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“…STRIPAK regulates SmKIN3 phosphorylation indirectly. In mammalian cells, Hippo comprises two kinases, GCK MST1/2 and NDR kinase LATS1/2 (27,28). Recently, it was shown that STRIPAK integrates upstream signals to control the activity of the SmKIN3 homolog MST1/2 for initiating Hippo signaling.…”

Section: Discussionmentioning

confidence: 99%

Targeted Quantification of Phosphorylation Sites Identifies STRIPAK-Dependent Phosphorylation of the Hippo Pathway-Related Kinase SmKIN3

Stein

Blank-Landeshammer

Märker

et al. 2021

mBio

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We showed recently that the germinal center kinase III (GCKIII) SmKIN3 from the fungus Sordaria macrospora is involved in sexual development and hyphal septation. Our recent extensive global proteome and phosphoproteome analysis revealed that SmKIN3 is a target of the striatin-interacting phosphatase and kinase (STRIPAK) multisubunit complex. Here, using protein samples from the wild type and three STRIPAK mutants, we applied absolute quantification by parallel-reaction monitoring (PRM) to analyze phosphorylation site occupancy in SmKIN3 and other septation initiation network (SIN) components, such as CDC7 and DBF2, as well as BUD4, acting downstream of SIN. For SmKIN3, we show that phosphorylation of S668 and S686 is decreased in mutants lacking distinct subunits of STRIPAK, while a third phosphorylation site, S589, was not affected. We constructed SmKIN3 mutants carrying phospho-mimetic and phospho-deficient codons for phosphorylation sites S589, S668, and S686. Investigation of hyphae in a ΔSmkin3 strain complemented by the S668 and S686 mutants showed a hyper-septation phenotype, which was absent in the wild type, the ΔSmkin3 strain complemented with the wild-type gene, and the S589 mutant. Furthermore, localization studies with SmKIN3 phosphorylation variants and STRIPAK mutants showed that SmKIN3 preferentially localizes at the terminal septa, which is distinctly different from the localization of the wild-type strains. We conclude that STRIPAK-dependent phosphorylation of SmKIN3 has an impact on controlled septum formation and on the time-dependent localization of SmKIN3 on septa at the hyphal tip. Thus, STRIPAK seems to regulate SmKIN3, as well as DBF2 and BUD4 phosphorylation, affecting septum formation. IMPORTANCE Phosphorylation and dephosphorylation of proteins are fundamental posttranslational modifications that determine the fine-tuning of their biological activity. Involved in this modification process is the recently identified striatin-interacting phosphatase and kinase (STRIPAK) multisubunit complex, which is evolutionarily conserved from fungi to humans. STRIPAK functions as a macromolecular assembly communicating through physical interactions with other conserved signaling protein complexes to constitute larger dynamic protein networks. Its function is implied in many cellular processes, such as signal transduction pathways, growth, and cellular differentiation. We applied absolute quantification of protein phosphorylation by parallel-reaction monitoring (PRM) to analyze phosphorylation site occupancy in signaling components that are linked to the STRIPAK complex. Using the filamentous fungus Sordaria macrospora, we provide evidence for the phosphorylation-dependent role of the Hippo-like germinal center kinase SmKIN3, which controls septum formation, and localize it in a time-dependent manner on septa at the hyphal tip.

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An overview of signaling pathways regulating YAP/TAZ activity

Cited by 83 publications

References 128 publications

Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis

Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis

KIF4A enhanced cell proliferation and migration via Hippo signaling and predicted a poor prognosis in esophageal squamous cell carcinoma

Targeted Quantification of Phosphorylation Sites Identifies STRIPAK-Dependent Phosphorylation of the Hippo Pathway-Related Kinase SmKIN3

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