Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Cobbaut, Mathias; Karagil, Simge; Bruno, Lucrezia; Loza, María del Carmen Díaz de la; Mackenzie, Francesca E.; Stolinski, Michael; Elbediwy, Ahmed

doi:10.3390/cells9010151

Cited by 39 publications

(34 citation statements)

References 123 publications

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“…Among typical YAP/TAZ targets are several secretory factors, including amphiregulin, connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61), which are important in stromal interactions and niche formation of cancer metastasis [18][19][20][21][22].There is ample and rapidly growing literature on the mechanisms of YAP/TAZ regulation, particularly by the Hippo signaling pathway, which prohibits organ overgrowth through the regulation of cell proliferation and cell survival during normal development. Recent excellent and comprehensive reviews summarize this wealth of published information from different angles: from a protein structural perspective [23,24]; from the angle of tissue mechanics, microenvironment and cytoskeleton interactions [25][26][27]; from the aspect of DNA-binding protein partners of YAP/TAZ [28,29] and in the context of normal development [30]; specific cancers (i.e., of the breast [31], lung [32] liver [33], prostate [34], pancreas [35] and various pediatric cancers [36]) and other chronic and neurodegenerative diseases [37,38].The adaptation to microenvironments of different tissue architecture plays a particularly important role in bone cancers which tend to metastasize through the hematogenous route and home primarily to bone and lungs, which are organs of completely different stiffness, extracellular matrix composition and oxygen supply. It is therefore not unexpected that the YAP/TAZ signaling pathway is prominently involved in bone cancer pathogenesis and metastatic spread.…”

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confidence: 99%

“…There is ample and rapidly growing literature on the mechanisms of YAP/TAZ regulation, particularly by the Hippo signaling pathway, which prohibits organ overgrowth through the regulation of cell proliferation and cell survival during normal development. Recent excellent and comprehensive reviews summarize this wealth of published information from different angles: from a protein structural perspective [23,24]; from the angle of tissue mechanics, microenvironment and cytoskeleton interactions [25][26][27]; from the aspect of DNA-binding protein partners of YAP/TAZ [28,29] and in the context of normal development [30]; specific cancers (i.e., of the breast [31], lung [32] liver [33], prostate [34], pancreas [35] and various pediatric cancers [36]) and other chronic and neurodegenerative diseases [37,38].…”

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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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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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“…Cellular mechanotransduction has been demonstrated in the heart, and mechanical forces are greatly increased in AS [45,46], suggesting the potential influence of mechanotransduction during myocardial remodeling. Among various pathways that are involved in the mechanical signaling, the Hippo pathway and its regulation of the YAP/TAZ protein complex have been highlighted to play a central role [46][47][48]. The core regulators of the Hippo pathways, including MST1/2, SAV1, TAO-family kinases (TAO), and MAP 4 K kinases, activate LATS1 and LATS2 kinases, which subsequently phosphorylate YAP/TAZ, thereby stimulating proteolysis of the YAP/ TAZ complex and limiting its transcription regulatory capacity.…”

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confidence: 99%

H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

et al. 2020

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Background: H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes.

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“…The Hippo signaling cascade plays various roles in cancer, including the regulation of cell proliferation and apoptosis, progression regulation of stem cell self-renewal, drug resistance, and metastasis [ 5 – 7 ]. The mammalian Ste20-like serine/threonine kinase1/2 (MST1/2) in this cascade can be phosphorylated by external stimuli such as KIBRA/NF2 and TAO kinases [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Hippo Pathway and CD133 in Radiation Resistance in Small-Cell Lung Cancer

Yang

et al. 2021

Journal of Oncology

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Although the Hippo pathway and CD133 have been reported to play pertinent roles in a variety of cancer, knowledge about their contribution to radiation resistance in small-cell lung cancer (SCLC) is limited. In this first-of-a-kind study, we have reported the expression of key Hippo pathway proteins in SCLC patients by immunohistochemical staining. We assessed the involvement of yes-associated protein 1 (YAP1) in radiation resistance by Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, we analysed the impact of CD133 on radiotherapy for SCLC. The mammalian Ste20-like serine/threonine kinase 2(MST2), pMST2, and pYAP1 in the Hippo pathway were not significantly associated with the disease stage and survival time in patients with SCLC. However, the pYAP1 expression showed some significance in the “YAP/TAZ subgroup” of SCLC patients. The proportion of CD133 in the SCLC cells was controlled by the YAP1 expression. The CD133 and YAP1 levels were significantly correlation with each other in tissues of SCLC patients. We sorted and isolated the CD133+ and CD133−cells in H69 and found that the cell surface glycoprotein may be associated with the radiation resistance of SCLC.In summary, we have firstly reported the expression of key Hippo pathway proteins in SCLC patients. Furthermore, we also identified that CD133 may be controlled by the expression of YAP1 in the Hippo pathway and that CD133 may be associated with the radiation resistance of SCLC.

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Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Cited by 39 publications

References 123 publications

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

Evaluation of Hippo Pathway and CD133 in Radiation Resistance in Small-Cell Lung Cancer

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