YAP1 overexpression

The present study demonstrated that YAP1 positively regulates aerobic glycolysis by inhibiting EGLN2 expression, which results in an increased HIF-1α protein level and transcriptional activity. YAP1 was positively regulated and significantly correlated with HIF-1α-targeted glycolytic genes, including glucose transporter type 1(GLUT1), hexokinase2 (HK2) and lactate dehydrogenase A (LDHA). Elevated YAP1 expression and concomitant downregulation of EGLN2 contributed to poor survival in patients with pancreatic cancer. Our results suggest that YAP1 may be a promising predictive marker and treatment target for human pancreatic cancer.

Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment.

Several studies have demonstrated that YAP1 is overexpressed in bladder cancer and is involved in adverse outcomes such as bladder cancer occurrence, progression, resistance to cisplatin and the recurrence of tumours...In addition, this study further explored the potential of YAP1 in the diagnosis and treatment of bladder cancer. This study aimed to explore the potential mechanism of YAP1 in the treatment of bladder cancer.

PLOD2 exerted pro‑oncogenic effects on CESC through the p53 pathway by binding to YAP1. These findings provide new perspectives for the future study of PLOD2‑targeted therapy for CESC.

In vivo studies also confirmed that GL-V9 exerts anti-tumor effects by suppressing YAP1 expression, while also activating autophagy and inducing mitochondrial apoptosis in BXPC-3-bearing BALB/c nude mice. Our findings underscore the importance of autophagy-mediated YAP1 degradation in PDAC, providing a novel molecular rationale (GL-V9) as a promising treatment for this disease.

Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.

Finally, DHA reduced GLUT1-aerobic glycolysis in HCC cells through YAP1 and prevented the binding of YAP1 and HIF-1α. Collectively, our study revealed the mechanism of DHA inhibiting glycolysis in HCC cells from a perspective of a positive feedback loop involving YAP1 and GLUT1 mediated-aerobic glycolysis and provided a feasible therapeutic strategy for targeting enhanced aerobic glycolysis in HCC.

YAP1 knockdown also reduced the IC50 value following treatment with vincristine, daunorubicin, cyclophosphamide, and dexamethasone (p < 0.05). Disruption of the Hippo pathway attenuates the development of cALL by promoting cell proliferation, while suppressing apoptosis and drug sensitivity.

UHRF1 inhibition mitigates vascular endothelial cell injury and ameliorates AS progression in mice by regulating the SMAD7/YAP1 axis.

GSH, oxidized GSH species, total GSH content, and glutaminase activity in cisplatin-resistant CCAs with BBD treatment also decreased, while YAP1 overexpression countered BBD's effects. This study provides a scientific basis for BBD clinical application and provides a new direction for BBD biological mechanism research.

Taken together, these results illustrated that Tub B demonstrated great potential in inhibiting migration of HCC, and a portion of its impact can be attributed to the modulation of the Hippo-YAP pathway.

Importantly, circ_0051246 knockdown and miR-375 activation suppressed CSC tumorigenicity in vivo. This study highlights the promotion of circ_0051246-miR-375-YAP1 axis activation in GC progression and provides a scientific basis for research on the molecular mechanism of CSCs.

Our results suggest that ENO1 overexpression promotes cell growth and tumor progression by increasing the expression of YAP1 in PC. Further studies are required to understand the detailed mechanisms between ENO1 and YAP1 in PC.

Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib-induced toxicity...Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown-induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.

Moreover, we found that YAP1 enhanced EBV lytic reactivation induced by two known activators, 12-O-tetradecanoylhorbol-13-acetate (TPA) and sodium butyrate (NaB). These results indicated a bidirectional regulatory mechanism between EBV and YAP1 proteins, providing new experimental evidence for further understanding the regulation of EBV infection patterns and carcinogenic mechanisms in gastric cancer.

Among the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.

Collectively, the YAP1/RBM24/β-catenin axis plays a critical role in driving TNBC progression. RBM24 may represent a novel therapeutic target for TNBC treatment.

Inhibition of YAP expression reduced myeloid-derived suppressor cells (MDSCs) and influenced the immunosuppressive state, leading to radio resistance. These findings provide insights into the YAP-HIF-1α interaction and support YAP as a potential target for enhancing radiotherapy sensitivity in esophageal cancer.

To conclude, ZNF131 was highly expressed and acted as an oncogene in HCC. ZNF131, which was activated by YAP1, promoted HCC cell proliferation through transcriptional regulation of PAIP1.

Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.

Furthermore, Verteporfin (a small molecule inhibitor of YAP) interrupted the YAP-TEAD interaction and inhibited FAK phosphorylation, confirming that YAP can induce FAK phosphorylation in a TEAD-dependent manner...Silencing HMGB1 reversed YAP-induced FAK activation as well as cell proliferation and migration. Collectively, our results reveal a new signalling axis, YAP/HMGB1/FAK, in the regulation of cell proliferation and migration, and provide new insights into the crosstalk between Hippo signalling and cell proliferation.

In conclusion, ZFX knockdown protected mice from hypoxia-induced PAH injury. ZFX knockdown dramatically reduced RVSP and RV/(LV + S) in hypoxia-treated mice.

The findings suggest that YAP1 depletion in CAFs induces the downregulation of p-AKT signaling in melanoma cells through the N-cadherin-mediated interaction between melanoma cells and CAFs. The data underscore an important role of CAFs in regulating N-cadherin-mediated adhesion and signaling in melanoma and highlight that disentangling cadherin-mediated cell-cell interactions can potentially disrupt tumor-stroma interactions and reverse the tumor cell invasive phenotype.

Our study reveals the intricate transition between acinar and AD states in human pancreatic tissues. It unveils the complex interaction between the Hippo and TGF-β pathways during ADM, highlighting the pivotal role of YAP1/TAZ and SMAD4 in PDAC initiation.

YAP1 over-expression in CRC cells enhanced their migration and invasion significantly which can be reversed by AXL, CTGF, or CYR61 interference. The study suggested that YAP1 affected the prognosis of CRC patients and controlled the abilities of invasion and migration of CRC cells via its target genes AXL, CTGF, and CYR61.

Thus, we screened for inhibitors that repress YAP1 expression and identified multiple bromodomain and extra-terminal (BET) inhibitors, including NHWD-870, as hits. We identified a new vulnerability for MEK inhibitor-resistant melanomas, which activated Hippo pathway due to elevated YAP1 activity. Inhibition of BRD4 using BET inhibitors suppressed YAP1 expression and led to blunted melanoma growth when combined with treatment with the MEK inhibitor trametinib.

Collectively, these findings suggest that PKMYT1, functioning as a direct gene target regulated by YAP/TEAD1, could serve as a potential indicator of progression and prognosis in BLCA. Further, PKMYT1 could serve as a novel therapeutic target for BLCA.

The YAP inhibitor Verteporfin (VP) and the overexpression of YAP were used to investigate its potential relation with glioma...ORI reversed the effect of overexpression of YAP. Collectively, oridonin suppressed glioblastoma oncogenesis via the Hippo/YAP signaling pathway and could be a potential therapeutic target in the treatment of glioblastoma.

YAP1 could serve as a prognostic marker as well as a therapeutic target in patients with HR+HER2- breast cancer.

The results of MST and DARTS demonstrated direct binding between HC, YAP, and CNOT4. The above results indicated that HC inhibited the malignant progression of TNBC via CNOT4-mediated degradation and ubiquitination of YAP.

Overexpression of YAP in colon cancer cells led to increased cell viability, invasion, migration, and oxaliplatin resistance demonstrating that YAP plays a role in EMT...Knockdown of YAP by shRNA interference led to decreased cell invasion, migration, and drug resistance in colon cancer cells and reduced tumorigenesis in a mouse xenograft model. Finally, we established that YAP interacted with SDC2, and demonstrated that SDC2 mediated the YAP pathway through the EMT-related factors BMP4, CTGF and FOXM1.

In PC-3 and DU-145 cells, YAP1 overexpression vector, small-interfering RNA, specific inhibitor verteporfin, ferroptosis-inducer RSL3, SLC1A5-inhibitor V-9302, and GLS1-inhibitor CB-839 were used. Thus, inhibiting SLC1A5 or GLS1 activity could alleviate the antagonistic effect of YAP1 on the ferroptosis of RSL3-induced CRPC cells. In CRPC, the YAP1 level is high, which enters the nucleus and promotes the expressions of SLC1A5 and GLS1, thereby promoting cellular glutamine uptake and metabolism to generate glutamate and further synthesizing GSH, increasing GPX4 activity, improving cellular antioxidant capacity, and inhibiting cell death.

High expression of YAP1 leads to poor prognosis in EC by regulation of stemness. YAP1 plays an important role in the prognosis of patients with EC by regulation of stemness.

Taken together, our results demonstrate the negative regulatory function of YAP in Tax activation of HTLV-1 transcription. It may achieve sufficient transcriptional repression to maintain persistent infection and long-term latency of HTLV-1 in the host cells.

Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.

Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.

YAP-1 expression was significantly higher in poorly and moderately differentiated invasive squamous cancer than in well-differentiated carcinomas. Overexpression of YAP-1 within the margin of preinvasive and invasive OSSN, but not in the neighboring normal epithelium, indicates that it plays a role in the development and progression of OSSN.

The bioinformatics and luciferase report data validated that both miR-214-3p and YAP1 were hsa_circ_0014784 binding partners. The overexpression of YAP1 reversed the migration, proliferation, and epithelial - mesenchymal transition (EMT) of PC cells and the angiogenic differentiation of HUVECs after miR-214-3p overexpression. Taken together, our study found that hsa_circ_0014784 downregulation decremented invasion, proliferation, EMT, and angiogenesis of PC by regulating miR-214-3p/YAP1 signaling.

In summary, we successfully constructed an OSMI-1's folate-targeted diselenide-responsive liposome, which exhibited well targetability and efficacy against colon cancer tissue with low toxicity to normal tissue. Furthermore, we demonstrating that OGT inhibition can reduce the YAP's O-GlcNAcylation and enhance its phosphorylation thus suppress YAP nuclear translocation, to suppress the development of colon cancer. Our research provides a brand new targeted therapy for colon cancer, with significant application value and broad development prospects.

KIF4A upregulation correlates with poor prognosis of UBC. Knockdown of KIF4A inhibits proliferation, migration, and invasion of UBC cells while inducing apoptosis possibly through dephosphorylation of AKT, changes in EMT-related genes, and interaction with YAP1.

This review focuses on the role of YAP in OSCC in the context of cancer metastatic potential and highlights the latest findings about the heterogeneity of YAP expression and its nuclear transcription activity in oral cancer cell lines. The review also discusses the potential target of YAP in oral cancer therapy and the recent finding of the unprecedented role of the desmosomal cadherin desmoglein-3 (DSG3) in regulating Hippo-YAP signaling.

RNase R and Actinomycin D were used to test the stability of circ_0091579...Meanwhile, miR-1270 inhibitor could invert the negative regulation effect of circ_0091579 silencing on YAP1 expression. Circ_0091579 promoted HCC progression by regulating the miR-1270/YAP1 axis, and our study might offer novel biomarkers and therapeutic targets for HCC.