The TAZ–miR-224–SMAD4 axis promotes tumorigenesis in osteosarcoma

Ma, Jianjun; Huang, Kai; Ma, Yan; Zhou, Menglu; Fan, Shunwu

doi:10.1038/cddis.2016.468

Cited by 30 publications

(28 citation statements)

References 43 publications

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“…It is therefore not surprising that YAP/TAZ play an important role in osteogenesis. Moreover, incorporation of α-smooth muscle actin in contractile stress fibers of MSC favor osteogenic differentiation in a YAP-dependent fashion [150]. In fact, YAP depletion was shown to downregulate the expression of osteogenic genes and of focal adhesion components paxillin, β-1 integrin and zyxin in human MSC in vitro [151].…”

Section: Yap and Taz As Regulators Of Osteogenesismentioning

confidence: 99%

“…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]. Thus, it is possible that YAP and TAZ serve distinct functions in osteosarcoma pathogenesis and progression.…”

Section: Yap/taz In Osteosarcomamentioning

confidence: 99%

“…These data suggest that, while fluctuations in EWS-FLI1 may be involved in the initiation of the metastatic process by inducing EMT/MET-like processes involving YAP/TAZ, persistent YAP/TAZ activity is selected during Ewing sarcoma metastasis. Yet, nuclear YAP and TAZ are only infrequently found in Ewing sarcoma immunohistochemistry (20% and 15%, respectively) [150].…”

Section: Yap/taz In Ewing Sarcomamentioning

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 and Taz As Regulators Of Osteogenesismentioning

confidence: 99%

Section: Yap/taz In Osteosarcomamentioning

confidence: 99%

Section: Yap/taz In Ewing Sarcomamentioning

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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“…Apart from downstream target proteins, several recent studies have revealed that YAP and TAZ also regulate the expression of microRNAs [ 89 , 282 , 362 , 363 , 364 , 365 , 366 , 367 ]. Bertero and colleagues found that YAP/TAZ activation promoted the expression of the miR-130/301 family, which in turn enhanced collagen deposition and ECM remodeling to further enhance YAP activity [ 365 ].…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

“…YAP and TAZ regulate miR-25, miR-93, and miR-106b to promote non-small cell lung cancer proliferation [ 363 ], and these miRNAs are overexpressed in lung, breast, and head and neck cancers [ 363 ]. TAZ can regulate miR135b and miR224 to promote EMT and tumorigenesis in osteosarcoma [ 366 , 367 ]. Evidence also shows that YAP can repress miRNA processing in cancer cells [ 368 ], and that YAP and TAZ can also regulate pre-miRNA processing through Dicer [ 369 ].…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

Warren

Xiao

2018

Cancers

142

131

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Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) have both emerged as important drivers of cancer progression and metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive human cancers. There is abundant experimental evidence demonstrating that YAP or TAZ activation promotes cancer formation, tumor progression, and metastasis. In this review we summarize the evidence linking YAP/TAZ activation to metastasis, and discuss the roles of YAP and TAZ during each step of the metastatic cascade. Collectively, this evidence strongly suggests that inappropriate YAP or TAZ activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ activation is a promising strategy for the treatment of metastatic disease. To this end, we also discuss several potential strategies for inhibiting YAP/TAZ activation in cancer and the challenges each strategy poses.

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TAZ upregulates MIR‐224 to inhibit oxidative stress response in multiple myeloma

Abegunde

Grieve²,

Reiman

2023

Cancer Reports

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BackgroundOxidative stress within the bone marrow niche of multiple myeloma contributes to disease progression and drug resistance. Recent studies have associated the Hippo pathway with miRNA biogenesis and oxidative stress in solid tumors. Oxidative stress and miRNA pathway inter‐relates in several cancers. Our group recently showed that TAZ functions as a tumor suppressor in MM. However, the role of TAZ in oxidative stress in MM is unknown.AimsWe sought to examine the role of TAZ in myeloma cells' response to BM oxidative stress. We postulated that TAZ might be associated with an oxidative stress phenotype and distinct miRNA signature in MM.Methods and ResultsUsing human myeloma cell lines and clinical samples, we demonstrate that TAZ promotes myeloma cells' sensitivity to oxidative stress and anticancer‐induced cytotoxicity by inducing miR‐224 to repress the NRF2 antioxidant program in MM. We show that low expression of TAZ protein confers an oxidative stress‐resistant phenotype in MM. Furthermore, we provide evidence that overexpression of miR‐224 in myeloma cells expressing low amounts of TAZ protein inhibits cell growth and enhances sensitivity to anti‐myeloma therapeutics.ConclusionOur findings uncover a potential role for TAZ in oxidative stress response in MM via the miR‐224‐NRF2 molecular pathway. This provides the scientific ground to explore miR‐224 as a potential molecular target to modify TAZ expression and enhance myeloma sensitivity to treatment.

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The TAZ–miR-224–SMAD4 axis promotes tumorigenesis in osteosarcoma

Cited by 30 publications

References 43 publications

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

TAZ upregulates MIR‐224 to inhibit oxidative stress response in multiple myeloma

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