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BACKGROUND: Craniofacial skeletal deformities can be addressed by applying tensile force to sutures to prompt sutural bone formation. The intricate process of mechanical modulation in craniofacial sutures involves complex biomechanical signal transduction. The small GTPase Ras homolog gene family member A (RhoA) functions as a key mechanotransduction protein, orchestrating the dynamic assembly of the cytoskeleton by activating the Rho-associated coiled-coil containing protein kinase (ROCK). Transcriptional coactivator with PDZ-binding motif (TAZ) serves as a crucial mediator in the regulation of genes and the orchestration of biological functions within the mechanotransduction signaling pathway. However, the role of RhoA/ROCK-TAZ in trans-sutural distraction osteogenesis has not been reported. METHODS: We utilized pre-osteoblast-specific RhoA deletion mice to establish an in vivo calvarial trans-sutural distraction model and an in vitro mechanical stretch model for pre-osteoblasts isolated from neonatal mice. Micro-CT and histological staining were utilized to detect the formation of new bone in the sagittal suture of the skull as well as the activation of RhoA, Osterix and TAZ. The activation of ROCK-limk-cofilin and the nuclear translocation of TAZ in pre-osteoblasts under mechanical tension were detected through Western blot, qRT-PCR, and immunofluorescence. RESULTS: The osteogenic differentiation of pre-osteoblasts was facilitated by mechanical tension through the activation of RhoA and Rho-associated kinase (ROCK), while ablation of RhoA impaired osteogenesis by inhibiting pre-osteoblast differentiation after suture expansion. Furthermore, inhibiting RhoA expression could block tensile-stimulated nuclear translocation of TAZ by preventing F-actin assembly through ROCK-LIM-domain kinase (LIMK)-cofilin pathway. In addition, the TAZ agonist TM-25659 could attenuate impaired osteogenesis caused by ablation of RhoA in pre-osteoblasts by increasing TAZ nuclear accumulation. CONCLUSIONS: This study demonstrates that mechanical stretching promotes the osteogenic differentiation of pre-osteoblasts in trans-sutural distraction osteogenesis, and this process is mediated by the RhoA/ROCK-TAZ signaling axis. Overall, our results may provide an insight for potential treatment strategies for craniosynostosis patients through trans-sutural distraction osteogenesis.

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Bone fracture healing is regulated by mechanobiological cues. Both, extracellular matrix (ECM) deposition and microvascular assembly determine the dynamics of the regenerative processes. Mechanical instability as by inter-fragmentary shear or compression is known to influence early ECM formation and wound healing. However, it remains unclear how these external cues shape subsequent ECM and microvascular network assembly. As transcriptional coactivators, the mechanotransducers yes-associated protein 1 (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) translate physical cues into downstream signaling events, yet their role in sprouting angiogenesis into the hematoma after injury is unknown. Using bone healing as model system for scar-free regeneration, the role of endothelial YAP/TAZ in combination with tuning the extrinsic mechanical stability via fracture fixation is investigated. Extrinsically imposed shear across the gap delayed hematoma remodeling and shaped the morphology of early collagen fiber orientations and microvascular networks, suggesting that enhanced shear increased the nutrient exchange in the hematoma. In contrast, endothelial YAP/TAZ deletion has little impact on the overall vascularization of the fracture gap, yet slightly increases the collagen fiber deposition under semi-rigid fixation. Together, these data provide novel insights into the respective roles of endothelial YAP/TAZ and extrinsic mechanical cues in orchestrating the process of bone regeneration.

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Excessive osteoclast activation is a leading cause of osteoporosis. Therefore, identifying molecular targets and relevant pharmaceuticals that inhibit osteoclastogenesis is of substantial clinical importance. Prior research has indicated that transcriptional coactivator with PDZ-binding motif (TAZ) impedes the process of osteoclastogenesis by engaging the nuclear factor (NF)-κB signaling pathway, thereby suggesting TAZ activation as a potential therapeutic approach to treat osteoporosis. (R)-PFI-2 is a novel selective inhibitor of SETD7 methyltransferase activity, which prevents the nuclear translocation of YAP, a homolog of TAZ. Therefore, we hypothesized that (R)-PFI-2 could be an effective therapeutic agent in the treatment of osteoporosis. To test this hypothesis and explore the underlying mechanism, we first examined the impact of (R)-PFI-2 on osteoclastogenesis in bone marrow macrophages (BMMs) in vitro. (R)-PFI-2 treatment inhibited TAZ phosphorylation induced by NF-κB, thereby enhancing its nuclear localization, protein expression, and activation in BMMs. Moreover, (R)-PFI-2-induced TAZ activation inhibited osteoclast formation in a dose-dependent manner, which involved inhibition of osteoclastogenesis through the TAZ and downstream NF-κB pathways. Furthermore, (R)-PFI-2 inhibited osteoclastogenesis and prevented ovariectomy-induced bone loss in vivo in a mouse model. Overall, our findings suggest that TAZ activation by (R)-PFI-2 inhibits osteoclastogenesis and prevents osteoporosis, indicating an effective strategy for treating osteoclast-induced osteoporosis.

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The survival of non-small cell lung cancer (NSCLC) patients has improved in the last decade as a result of introducing new therapeutics, such as immune checkpoint inhibitors, in the clinic. Still, some NSCLC patients do not benefit from these therapies due to intrinsic resistance or the development of acquired resistance and their malignant disease progresses. Further research on the molecular underpinnings of NSCLC pathobiology is required in order to discover clinically relevant molecular targets that regulate tumor immunity and to develop reasonable therapeutic combinations that will promote the efficacy of immune checkpoint inhibitors. Yes-associated Protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the final effectors of the Hippo signaling transduction pathway, are emerging as key players in NSCLC development and progression. Herein, we overview studies that have investigated the oncogenic role of YAP/TAZ in NSCLC, focusing on immune evasion, and highlight the therapeutic potential of combining YAP/TAZ inhibitory agents with immune checkpoint inhibitors for the management of NSCLC patients.

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Aggressive cancers, such as triple-negative breast cancer (TNBC), are mostly fatal because of their potential to metastasize to distant organs. Cancer cells acquire various abilities to metastasize, including resistance to anoikis, an apoptotic cell death induced by loss of anchorage to the extracellular matrix. Transcriptional coactivator with PDZ binding motif (TAZ) and Yes-associated protein (YAP), the downstream effectors of the Hippo pathway, regulate cell- and tissue-level architectures by responding to mechanical microenvironments of cells, including the cell-extracellular matrix interaction. The Hippo pathway is frequently disrupted in cancer cells, and TAZ and YAP are irrelevantly activated, potentially resulting in anchorage-independent survival/proliferation of cancer cells and metastatic progression. The study aims to investigate the roles of TAZ and YAP in anoikis resistance in basal-like (BL) TNBC cells, which comprise a major subtype (>70%) of TNBC. We found that TAZ and YAP had nonredundant roles in anchorage-independent cancer cell survival or anoikis resistance. Particularly, TAZ was indispensable for anoikis resistance in BL-TNBC cells but not for survival of non-transformed mammary epithelial cells (MECs). In contrast, YAP, a paralog of TAZ, was indispensable for survival of both non-transformed MECs and cancer cells. Therefore, TAZ might be a preferable therapeutic target against dissemination of aggressive cancer cells without killing normal cells. Interestingly, TAZ was abnormally stabilized in BL-TNBC cells under non-adherent conditions, which promoted anoikis resistance. Furthermore, OTUB1, a deubiquitinating enzyme, was responsible for the stabilization of TAZ in detached BL-TNBC cells. Importantly, simultaneous high expression of TAZ and OTUB1 was associated with poor prognosis in BC. Thus, OTUB1 has emerged as a potentially druggable target. Successful inhibition of OTUB1 enzymatic activity is expected to downregulate TAZ and eventually prevents metastasis of aggressive cancers, such as BL-TNBC.

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Steroidogenesis in ovarian granulosa cells is regulated by the follicle-stimulating hormone (FSH) via transcriptional regulation of its related genes. We herein showed the involvement of the Hippo pathway in this regulation. In KGN granulosa cell, repression of YAP/TAZ activity induced the expression of CYP11A1, HSD3B2, and CYP19A1 in a TEAD-dependent manner without cAMP stimulation. A selective inhibitor of p38 MAP kinase, suppressed YAP/TAZ knockdown-indued the expression of these genes, suggesting this signal could be involved. The expression of these genes was induced by 8Br-cAMP, whereas that of CYR61 and ADATS1, typical YAP/TAZ-TEAD target genes, was suppressed, suggesting that the cellular signaling of cAMP reduced YAP/TAZ-TEAD activity. The constitutively active mutant YAP canceled the FSH- and 8Br-cAMP-mediated induction of these genes in primary rat granulosa and KGN cells, respectively. Moreover, regulation of steroidogenesis-related genes by YAP/TAZ-TEAD was independent of steroidogenic factor 1, a master gene regulator of steroidogenesis. These results suggest that YAP/TAZ-TEAD is a negative regulator of steroidogenesis and that suppression of YAP/TAZ-TEAD activity by FSH is involved in ovarian steroidogenesis.

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Bone marrow mesenchymal stem cells (BM-MSCs), with the properties of self-renewal and pluripotency, can migrate to the tumor sites and exert complex effects on tumor progression and communications by releasing exosomes. However, to our knowledge, only a few studies have reported the effects of BM-MSCs exosomes on breast cancer cells development. Here, utilizing exosomes isolated from in vitro BM-MSCs, we systematically investigated this issue in a breast cancer cell line. In this study, we found that BM-MSCs exosomes are actively incorporated by breast cancer cell MDA-MB-231 cells and subsequently promote MDA-MB-231 cells proliferation and migration. Mechanistically, we further found Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) which are Hippo signaling components were involved in this promoting progress. Consistently, YAP and TAZ knockdown could significantly reverse breast cancer cells proliferation and migration improved by BM-MSCs exosomes. Taken together, our findings demonstrated a new mechanism through which BM-MSCs-derived exosomes may contribute to breast cancer cells proliferation and migration, which might provide an evidence for novel drug discovery based on exosomes and Hippo signaling.

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During placentation, placental cytotrophoblast (CT) cells differentiate into syncytiotrophoblast (ST) cells and extravillous trophoblast (EVT) cells. In the placenta, the expression of various genes is regulated by the Hippo pathway through a transcription complex, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-TEA domain transcription factor (TEAD) (YAP/TAZ-TEAD) activity. YAP/TAZ-TEAD activity is controlled by multiple factors and signaling, such as cAMP signaling. cAMP signaling is believed to be involved in the regulation of trophoblast function but is not yet fully understood. Here we showed that YAP/TAZ-TEAD expressions and their activities were altered by cAMP stimulation in BeWo cells, a human choriocarcinoma cell line. The repression of YAP/TAZ-TEAD activity induced the expression of ST-specific genes without cAMP stimulation, and transduction of constitutively active YAP, i.e. YAP-5SA, resulted in the repression of 8Br-cAMP-induced expressions of ST-specific genes in a TEAD-dependent manner. We also investigated the role of YAP/TAZ-TEAD in maintaining CT cells and their differentiation into ST and EVT cells using human trophoblast stem (TS) cells. YAP/TAZ-TEAD activity was involved in maintaining the stemness of TS cells. Induction or repression of YAP/TAZ-TEAD activity resulted in marked changes in the expression of ST-specific genes. Using primary CT cells, which spontaneously differentiate into ST-like cells, the effects of YAP-5SA transduction were investigated, and the expression of ST-specific genes was found to be repressed. These results indicate that the inhibition of YAP/TAZ-TEAD activity, with or without cAMP stimulation, is essential for the differentiation of CT cells into ST cells.

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Systemic sclerosis (SSc) is a heterogeneous disease with skin fibrosis. Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) is associated with fibrotic response. This work attempted to determine the precise mechanism of YAP/TAZ in SSc. Single-cell sequencing (scRNA-seq) was used to analyse the differential gene expression between SSc patients and healthy volunteers, showing that the YAP/TAZ signalling pathway was enriched in the fibroblasts of SSc patients. Subsequently, enzyme-linked immunosorbent assay and immunohistochemical analyses were conducted to examine the levels of YAP and TAZ in mild and severe SSc patients. YAP and TAZ were highly expressed in the serum and skin tissues of mild and severe SSc patients, especially severe SSc patients. Additionally, an SSc mouse model was induced by bleomycin, and the impacts of YAP/TAZ knockdown on the pathological changes in skin and lung tissues were detected by haematoxylin and eosin staining and Masson staining. Knockdown of YAP and TAZ inhibited α-SMA mRNA and protein expression in skin and lung tissues of SSc mice. Inhibition of YAP and TAZ reduced skin inflammation and thickness and repressed lung inflammation and fibrosis in SSc mice. Importantly, knockdown of YAP and TAZ synergistically inhibited inflammation and fibrosis in skin and lung tissues in SSc mice. In conclusion, this work demonstrated that knockdown of YAP and TAZ exerted a synergistic effect on alleviating SSc in mice. Thus, this work suggests that YAP/TAZ is a potential target for SSc treatment.

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The prevalence of liver disease has been increasing worldwide. Moreover, the burden of end-stage liver disease, including cirrhosis and liver cancer, is high because of high mortality and suboptimal treatment. The pathological process of liver disease includes steatosis, hepatocyte death, and fibrosis, which ultimately lead to cirrhosis and liver cancer. Clinical and preclinical evidence indicates that non-neoplastic liver diseases, particularly cirrhosis, are major risk factors for liver cancer, although the mechanism underlying this association remains unclear. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional activators that regulate organ size and cancer development. YAP and TAZ play important roles in liver development, regeneration, and homeostasis. Abnormal YAP and TAZ levels have also been implicated in non-neoplastic liver diseases (e.g., non-alcoholic fatty liver disease, alcoholic liver disease, liver injury, and liver fibrosis). Here, we review recent findings on the roles of YAP and TAZ in non-neoplastic liver diseases and discuss directions for future research. This review provides a basis for the study of non-neoplastic liver diseases.

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The podocyte is an important component of the glomerular filtration barrier, and maintenance of the integrity of its highly specified structure and function is critical for normal kidney function. Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are two crucial effectors of the Hippo signaling pathway, and recent studies have shown that podocyte-specific YAP deletion causes podocyte apoptosis and the development of focal segmental glomerulosclerosis followed by progressive renal failure. In the present study, we investigated a potential role of the YAP paralog TAZ in podocytes. TAZ was found to be constitutively active in podocytes, and mice with podocyte-specific deletion of TAZ (TazpodKO) developed proteinuria starting at 4 wk of age and had increased podocyte apoptosis. Using primary cultured podocytes or immortalized mouse podocytes from Tazflox/flox mice, we found that TAZ is a transcriptional activator for TEAD-dependent expression of synaptopodin, zonula occludens-1, and zonula occludens-2. This is the first study to determine that TAZ plays an important role in the maintenance of the structure and function of podocytes.NEW & NOTEWORTHY Podocytes play an important role in maintaining the integrity of the structure and function of the kidney. We observed that mice with selective deletion of transcriptional coactivator with PDZ-binding motif (TAZ) in podocytes developed proteinuria. TAZ is constitutively active and critical for expression of synaptopodin, zonula occludens-1, and zonula occludens-2 in podocytes. The findings of this study implicate TAZ as an important mediator of podocyte structural integrity and provide further insights into the role of Hippo-Yes-associated protein/TAZ in podocyte biology.

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Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide, with high incidence and mortality. However, the exact mechanisms leading to HCC development remain unclear. The cores of the Hippo signaling pathway consist of a kinase cascade to transmit signals, which inhibits the transcriptional coactivator translocate into the nucleus and reduces the transcription of downstream proliferation-related genes. Hippo signaling pathway regulates liver development and regeneration after liver resection, and it is also related to the occurrence of HCC. The Hippo pathway regulates proliferation, apoptosis, metastasis, autophagy, metabolic reprogramming of HCC cells, affects the tumor immune microenvironment, and participates multiple-drug resistance. Further study on the role of Hippo signaling pathway in HCC is important to develop new therapeutic targets.

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Owing to an error that was made during the production stages of the above review article, what was actually Fig. 2 was inadvertently duplicated on p. 7 as Fig. 9. Fig. 9 as it should have appeared in the review is shown below. The Editor apologizes to the authors for this error, and regrets any inconvenience caused to the readership. [the original article was published in Molecular Medicine Reports 24: Article no. 506, 2021; DOI: 10.3892/mmr.2021.12145].

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Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis is gaining recognition, much remains unknown about various genetic and non-genetic determinants of ferroptosis. Hippo signaling pathway is an evolutionarily conserved pathway that responds to various environmental cues and controls organ size, cell proliferation, death, and self-renewal capacity. In cancer biology, Hippo pathway is a potent tumor suppressing mechanism and its dysregulation contributes to apoptosis evasion, cancer development, metastasis, and treatment resistance. Hippo dysregulation leads to aberrant activation of YAP and TAZ, the two major transcription co-activators of TEADs, that induce the expression of genes triggering tumor-promoting phenotypes, including enhanced cell proliferation, self-renewal and apoptosis inhibition. The Hippo pathway is regulated by the cell-cell contact and cellular density/confluence. Recently, ferroptosis has also been found being regulated by the cellular contact and density. The YAP/TAZ activation under low density, while confers apoptosis resistance, renders cancer cells sensitivity to ferroptosis. These findings establish YAP/TAZ and Hippo pathways as novel determinants of ferroptosis. Therefore, inducing ferroptosis may have therapeutic potential for YAP/TAZ-activated chemo-resistant and metastatic tumor cells. Reciprocally, various YAP/TAZ-targeting treatments under clinical development may confer ferroptosis resistance, limiting the therapeutic efficacy.

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Stem cells receive cues from their physical and mechanical microenvironment via mechanosensing and mechanotransduction. These cues affect proliferation, self­renewal and differentiation into specific cell fates. A growing body of evidence suggests that yes­associated protein (YAP) and transcriptional coactivator with PDZ­binding motif (TAZ) mechanotransduction is key for driving stem cell behavior and regeneration via the Hippo and other signaling pathways. YAP/TAZ receive a range of physical cues, including extracellular matrix stiffness, cell geometry, flow shear stress and mechanical forces in the cytoskeleton, and translate them into cell­specific transcriptional programs. However, the mechanism by which mechanical signals regulate YAP/TAZ activity in stem cells is not fully understand. The present review summarizes the current knowledge of the mechanisms involved in YAP/TAZ regulation on the physical and mechanical microenvironment, as well as its potential effects on stem cell differentiation.

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BACKGROUND: Transcriptional coactivator with PDZ binding motif (TAZ) regulates multiple biological processes and has been found to be related to hepatocellular carcinoma (HCC). However, common signaling pathways downstream after TAZ knockdown may also be important. METHODS: TAZ was knocked down in an HCC cell line, and its potential target genes were analyzed. A decrease in the expression of zinc finger and SCAN domain-containing protein 31 (ZSCAN31) was observed. The difference in ZSCAN31 expression was evaluated, and its effect on survival in HCC patients who received surgical resection was determined. RESULTS: ZSCAN31 was over-expressed in HCC tissues and was associated with low overall survival (OS) in HCC patients after surgical resection. Analysis of tissue samples from 83 HCC patients who underwent surgical resection in our hospital produced similar results. High ZSCAN31 expression was significantly associated with tumor size. High expression levels of both TAZ and ZSCAN31 were related to poor OS. A positive correlation was identified between ZSCAN31 expression and TAZ expression, and the protein binding of ZSCAN31 and TAZ was confirmed by co-immunoprecipitation (Co-IP) assay using an HCC cell line. CONCLUSIONS: ZSCAN31 is associated with TAZ expression in HCC cells, and the targeting of ZSCAN31 and TAZ may represent a novel therapeutic approach in HCC.

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Vestigial-like 3 (VGLL3) is a member of the VGLL family, whose members serve as cofactors for TEA domain-containing transcription factors (TEADs). TEADs promote tissue and tumor development together with the cofactors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Although VGLL3 is involved in tumor cell proliferation, its relationship with TEADs and YAP/TAZ remains largely unknown. To close this research gap, here we established tumor cells stably expressing VGLL3 and found that they exhibit enhanced proliferation. Notably, YAP and TAZ were inactivated in the VGLL3-expressing cells, coinciding with activation of the Hippo pathway, which suppresses YAP/TAZ activities. VGLL3 in combination with TEADs promoted expression of the Hippo pathway components large tumor suppressor kinase (LATS2) and angiomotin-like 2 (AMOTL2). VGLL3 was highly expressed in malignant breast tumor cells and osteosarcoma cells, and VGLL3 knockdown increased nuclear localization of YAP and TAZ. Knockdown of LATS2 or AMOTL2, as well as VGLL3 knockdown, repressed proliferation of breast tumor cells. Together, these results suggest that VGLL3 together with TEADs promotes cell proliferation by activating the Hippo pathway through LATS2 and AMOTL2, leading to YAP/TAZ inactivation.

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OBJECTIVES: Polydatin (PD), extracted from Polygonum cuspidatum, has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/ß-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. MATERIALS AND METHODS: hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. RESULTS: In vitro, 30 µM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2, Osteopontin, DLX5, ß-catenin, TAZ, and Osteocalcin (OCN). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/ß-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. CONCLUSION: Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/ß-catenin pathway.

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Mechanical force across sutures is able to promote suture osteogenesis. Orthodontic clinics often use this biological characteristic of sutures to treat congenital cranio-maxillofacial malformations. However, the underlying mechanisms still remain poorly understood. Craniofacial sutures provide a special growth source and support primary sites of osteogenesis. Here, we isolated rat sagittal suture cells (rSAGs), which had mesenchymal stem cell characteristics and differentiating abilities. Cells were then subjected to mechanical tension (5% elongation, 0.5 Hz; sinusoidal waveforms) showing that mechanical tension could enhance osteogenic differentiation but hardly affect proliferation of rSAGs. Besides, mechanical tension could increase Rho-associated kinase (ROCK) expression and enhance transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation. Inhibiting ROCK expression could suppress tension-induced osteogenesis and block tension-induced upregulation of nuclear TAZ. In addition, our results indicated that TAZ had direct combination sites with runt-related transcription factor 2 (Runx2) in rSAGs, and knock-downed TAZ simultaneously decreased the expression of Runx2 no matter with or without mechanical tension. In summary, our findings demonstrated that the multipotency of rSAGs in vitro could give rise to early osteogenic differentiation under mechanical tension, which was mediated by ROCK-TAZ signal axis.

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Ferroptosis is a novel form of programmed cell death. We found that the ferroptosis sensitivity in renal and ovarian cancers are regulated by cell density through TAZ-EMP1-NOX4 and TAZ-ANGPTL4-NOX2 pathway, respectively. These findings reveal TAZ as a novel genetic determinant of ferroptosis. Triggering ferroptosis may have therapeutic potential for TAZ-activated tumors.