Integration of Hippo-YAP Signaling with Metabolism

Ibar, Consuelo; Irvine, Kenneth D.

doi:10.1016/j.devcel.2020.06.025

Cited by 108 publications

(89 citation statements)

References 138 publications

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“…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 . However, the relationship between KIF4A and the Hippo signaling pathway in ESCC is unclear.…”

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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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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“…Yap1, a key transcriptional cofactor that is negatively regulated by the Hippo pathway, is essential for the development and size control of multiple organs [ 34 , 35 ]. In addition, more diverse functions of the Hippo pathway have been recognized, including cell proliferation, differentiation, and migration [ 12 , 36 ]. Overexpression of Yap1 in mouse ESCs inhibits ESC differentiation and is sufficient to maintain stem cell characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…Lin28 is widely expressed in a number of tissues from embryo to adult, particularly in the nervous system [ 6 , 12 ]. In vivo study showed that Lin28a knockout leads to reduced neural progenitor cell proliferation and a small brain in mouse, whereas knockout of both Lin28a alleles and one Lin28b allele displays similar but more severe phenotypes than the control, demonstrating the redundant and critical roles of Lin28a/b in the nervous system development [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Lin28 Inhibits the Differentiation from Mouse Embryonic Stem Cells to Glial Lineage Cells through Upregulation of Yap1

Luo

Zou

Deng

et al. 2021

Stem Cells International

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The RNA-binding protein Lin28 regulates neurogliogenesis in mammals, independently of the let-7 microRNA. However, the detailed regulatory mechanism remains obscured. Here, we established Lin28a or Lin28b overexpression mouse embryonic stem cells (ESCs) and found that these cells expressed similar levels of the core pluripotent factors, such as Oct4 and Sox2, and increased Yap1 but decreased lineage-specific markers compared to the control ESCs. Further differentiation of these ESCs to neuronal and glial lineage cells revealed that Lin28a/b overexpression did not affect the expression of neuronal marker βIII-tubulin, but dramatically inhibited the glial lineage markers, such as Gfap and Mbp. Interestingly, overexpression of Yap1 in mouse ESCs phenocopied Lin28a/b overexpression ESCs by showing defect in glial cell differentiation. Inhibition of Yap1/Tead-mediated transcription with verteporfin partially rescued the differentiation defect of Lin28a/b overexpression ESCs. Mechanistically, we demonstrated that Lin28 can directly bind to Yap1 mRNA, and the induction of Yap1 by Lin28a in mESCs is independent of Let7. Taken together, our results unravel a novel Lin28-Yap1 regulatory axis during mESC to glial lineage cell differentiation, which may shed light on glial cell generation in vitro.

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“…Hub genes mainly include MAPK1, EP300, RHOA, PIK3CA and CBL. The Hippo/YAP pathway is involved in the growth, death and migration of vascular smooth muscle cells and endothelial cells, which may contribute to the vascular remodeling of SONFH [26]. The PI3K/Akt signaling pathway plays an essential role in stem cell-regulated cell survival, proliferation, migration and angiogenesis [27].…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of Urinary Exosomal Hsa-microRNA-200b-3p and Hsa-microRNA-206 in Patients of Steroid-induced Osteonecrosis of Femoral Head

Chen

Zhang

Liu

et al. 2020

Preprint

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Background:Urine exosomal microRNAs (miRNAs) play vital roles in the occurrence and development of various diseases. However, less is known about miRNAs in steroid-induced osteonecrosis of the femoral head (SONFH). Here, we aimed to determine the value of miRNAs in urinary exosomes in the diagnosis of SONFH.Methods:RNA was extracted from urinary exosomes from 9 SONFH patients and 9 hip osteoarthritis (HOA) patients with age and gender matched and then miRNAs were analyzed by next generation sequencing. Next, the putative target genes of dysregulated miRNAs were predicted by miRNA databases. Furthermore, GO function, KEGG pathway, miRNAs-mRNAs network and protein-protein interaction (PPI) network were also constructed to analyze potentially pathological mechanisms. qRT-PCR and area under curve (AUC) analysis were performed to determine the diagnostic value of miRNAs. This study was approved by ethics review board in 1st Affiliated Hospital, Guangzhou University of Chinese Medicine.Results:Intriguingly, 15 miRNAs including hsa-miR-200b-3p and hsa-miR-206 were significantly upregulated in exosomes from SONFH patients. Furthermore, qRT-PCR and area under curve (AUC) analysis of an independent cohort of 30 SONFH patients, 10 HOA patients and 10 healthy donors confirmed that hsa-miR-200b-3p and hsa-miR-206 were upregulated in SONFH samples which AUC values were 0.938 (95 % CI: 0.828-1) and 0.926 (95 % CI: 0.806-1) respectively. The enriched functions and pathways included Hippo, PI3K-Akt, TGF-β and Wnt signaling pathways. The top five hub genes (MAPK1, EP300, RHOA, PIK3CA, and CBL) were selected from PPI network, which consisted of 180 nodes and 518 edges. Conclusions:Collectively, our results showed that hsa-miR-200b-3p and hsa-miR-206 in urinary exosomes which might serve as non-invasive biomarkers for SONFH.

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Integration of Hippo-YAP Signaling with Metabolism

Cited by 108 publications

References 138 publications

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

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

Lin28 Inhibits the Differentiation from Mouse Embryonic Stem Cells to Glial Lineage Cells through Upregulation of Yap1

Up-Regulation of Urinary Exosomal Hsa-microRNA-200b-3p and Hsa-microRNA-206 in Patients of Steroid-induced Osteonecrosis of Femoral Head

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