A miR-135b-TAZ positive feedback loop promotes epithelial–mesenchymal transition (EMT) and tumorigenesis in osteosarcoma

Shen, Shuying; Huang, Kai; Wu, Yizheng; Ma, Yan; Wang, Jiying; Qin, Feiwei; Ma, Jianjun

doi:10.1016/j.canlet.2017.08.005

Cited by 51 publications

(44 citation statements)

References 45 publications

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“…Consistent with this finding, sublines of human osteosarcoma cell lines U2OS and HOS selected for gradually increasing migratory ability showed parallel increases in TAZ RNA and protein expression and of EMT markers N-cadherin, vimentin and SNAIL, while E-cadherin was gradually decreased. This phenotype was reversed by TAZ knockdown, while ectopically forcing TAZ expression promoted the EMT-like transition of osteosarcoma cell lines [196]. The study also provided experimental evidence that much of the phenotypically EMT promoting effect was mediated by the directly TAZ/TEAD-activated microRNA hsa-miR-135b predicted to target LATS2, APC and GSK3β 3´UTRs and thereby upregulating TAZ in a positive feedback loop.…”

Section: Yap/taz In Osteosarcomamentioning

confidence: 75%

“…While all these data are consistent with an important role of activated nuclear YAP in osteosarcoma, there is little data on the potential role of TAZ in human patients. In a small series of 16 human osteosarcomas, 13 showed TAZ expression higher than normal bone tissue or chondromas [196]. A recent study performed in dogs suggested that TAZ may be specifically associated with the proliferative and migratory ability of metastasis-derived osteosarcoma cells [197].…”

Section: Yap/taz In Osteosarcomamentioning

confidence: 98%

“…The study also provided experimental evidence that much of the phenotypically EMT promoting effect was mediated by the directly TAZ/TEAD-activated microRNA hsa-miR-135b predicted to target LATS2, APC and GSK3β 3´UTRs and thereby upregulating TAZ in a positive feedback loop. Hsa-miR-135b overexpression was demonstrated to increase osteosarcoma xenograft growth [196]. Likewise, hsa-miR-224 was described as a TAZ/TEAD directly-activated target gene that enhances the proliferation and tumorigenicity of osteosarcoma and was demonstrated to rescue the migration, invasion and tumorigenicity of osteosarcoma cells upon TAZ knockdown at least in part through targeting SMAD4 [150].…”

Section: Yap/taz In Osteosarcomamentioning

confidence: 99%

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The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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Section: Yap/taz In Osteosarcomamentioning

confidence: 75%

Section: Yap/taz In Osteosarcomamentioning

confidence: 98%

Section: Yap/taz In Osteosarcomamentioning

confidence: 99%

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The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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“…Currently, it is widely recognised that epithelial-mesenchymal transition (EMT) is the key process for promoting tumour cell invasion and metastasis (18). Several studies have revealed that EMT is involved in OS malignancy process (19,20). Thus, the effect of USP7 on EMT was evaluated.…”

Section: Activation Of the Wnt/β-catenin Signalling Pathway By Usp7mentioning

confidence: 99%

Ubiquitin‑specific protease 7 promotes osteosarcoma cell metastasis by inducing epithelial‑mesenchymal transition

Zeng

Zhao

et al. 2018

Oncol Rep

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Osteosarcoma (OS) is the most common primary malignant bone tumour among adolescents and young adults; however, its molecular pathogenesis has not been completely elucidated. Ubiquitin-specific protease 7 (USP7), a member of the deubiquitinating enzyme family, plays a role in the malignancy process of various cancer types by targeting the key oncoprotein; however, its biological function and mechanism in OS have not been elucidated. The present study demonstrated that USP7 expression in OS tumour tissues was markedly higher than that in the paired surrounding tissues, and high USP7 expression was positively correlated with the TNM stage and metastasis in patients with OS. Next, biological function assays demonstrated that USP7 knockdown markedly inhibited OS cell migration and invasion, whereas USP7 overexpression enhanced it. Notably, USP7 can directly bind with β-catenin to activate the Wnt/β-catenin signalling pathway and induce epithelial-mesenchymal transition (EMT) of OS cells. Overall, USP7 overexpression could promote OS cell metastasis by activating the Wnt/β-catenin signalling pathway by inducing EMT, suggesting that USP7 is a potential therapeutic target for OS.

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“…. In osteosarcoma cells, overexpression of miR-135b and TAZ (transcriptional coactivator with PDZ-binding motif) engaged in a positive feedback loop and promotes cell proliferation, as well as EMT (S Shen et al, 2017)…”

mentioning

confidence: 99%

Expression pattern of microRNAs related with response to trastuzumab in breast cancer

Yang

et al. 2019

Journal Cellular Physiology

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Background Although an immense effort has been made to develop a novel biomarker for response to trastuzumab, no reliable biomarkers are available to guide management, expect for HER2. The aim of this study was to examine the relationship between microRNA (miRNA) expression and resistance to trastuzumab. Methods Differentially expressed miRNAs between trastuzumab‐resistant and trastuzumab‐sensitive cell lines were analyzed using microarrays. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to determine the functions of differentially expressed miRNA and their targeted genes. Furthermore, the protein–protein interactions (PPI) network was analyzed. Serum samples were collected from patients with HER2‐positive breast cancer who were treated with trastuzumab. We validated the miRNAs expression levels by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in these serums. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the miRNA. Results Using miRNA microarrays, 151 miRNAs that significant differentially expressed between the trastuzumab‐resistant and sensitive cells were identified, including 46 upregulated and 105 downregulated miRNAs. Results of real‐time PCR confirmed seven miRNAs in cell lines. PI3K‐Akt signaling pathway was involved in regulating biological function according to KEGG analysis. Compared with the serums of trastuzumab‐sensitive patients, three miRNAs, namely miR‐200b, miR‐135b, and miR‐29a, were identified to be upregulated, and miR‐224 was downregulated in the trastuzumab‐resistant serums. ROC analysis showed that four miRNAs were correlated with trastuzumab resistance. Furthermore, three subnetwork modules of PPI network were obtained. Conclusion The results indicated that miRNAs were reliable predictive biomarkers for response to trastuzumab.

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A miR-135b-TAZ positive feedback loop promotes epithelial–mesenchymal transition (EMT) and tumorigenesis in osteosarcoma

Cited by 51 publications

References 45 publications

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Ubiquitin‑specific protease 7 promotes osteosarcoma cell metastasis by inducing epithelial‑mesenchymal transition

Expression pattern of microRNAs related with response to trastuzumab in breast cancer

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