In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Previous studies have shown that chlorpromazine (CPZ) can inhibit YAP1 expression...Collectively, our findings indicate that FOXP3 competitively binds TEAD4 to regulate YAP1 localization in the nucleus and cytoplasm to suppress NPC progression. Consequently, FOXP3 may be a prognostic indicator for HNSCC.

Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

For this purpose, expression levels of radioresistance markers Yap-1 and Hsp90 were evaluated after treatment with HF-GKRT, and this was compared with single fraction Gamma Knife radiation therapy (SF-GKRT) in U87MG primary human glioblastoma cell line model. This would help design a novel radiation therapy regimen for glioblastoma patients by reducing the risk of radioresistance.

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.

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.

No abstract available

Our work suggests that the novel signaling axis circSETD2/HuR/YAP1 plays an important role in BC progression. The molecular mechanism underlying this signaling axis may provide a potential therapeutic target for BC treatment.

These results suggested that YAP1 suppression was sensitized to anti-PD-1 treatment and inhibited autophagy activity in liver tumor cells. YAP1 is a promising target for improving the efficacy of anti-PD-1 immunotherapy in HCC.

YAP1 inhibitor administration counteracted ADAM12's function in promoting CRC cell growth, migration, invasion and increasing CTGF, Cyr61 and Birc5 expression. Implications: Our study indicates that ADAM12 facilitates CRC progression through suppressing Hippo pathway activity, and that ADAM12 is the candidate therapeutic target and prognostic biomarker for CRC patients.

GPRC5A interacts with the Hippo pathway to promote the progression of pancreatic cancer. These findings reveal an important crosstalk model and provide potential targets for pancreatic cancer therapy.

YAP1 inhibition could trigger ICD and is a potential approach to potentiating the therapeutic efficacy of radiotherapy and anti-PD1 immunotherapy.

Consistently, verteporfin, YAP1 inhibitor, decreased TGF-β and IFN-γ in liver tumor niche and exhausted CD8 T cell in the spleen...Mechanistically, YAP1 knockdown suppressed PD-L1 expression, which was involved in JAK1/STAT1, 3 pathways. Finally, DHA inhibited YAP1 expression, which not only inhibited liver tumor proliferation but also break the immunosuppressive niche in liver tumor tissues and improve the effect of anti-PD-1 therapy.

Inhibition of TEAD binding to YAP1 in mammalian cells was also observed. Several compounds inhibited the cell viability of sarcoma, hepatocellular carcinoma, glioblastoma, and breast cancer cells with single-digit micromolar IC values.

P1, N=15, Completed, Ionis Pharmaceuticals, Inc. | Recruiting --> Completed | N=102 --> 15 | Trial completion date: Jun 2023 --> Oct 2022 | Trial primary completion date: Jun 2023 --> Oct 2022

Moreover, we also analyzed the influence of UHRF1 on cisplatin (DDP) sensitivity of SCLC...UHRF1 plays an oncogenic role in SCLC by modulating YAP1. Therefore, UHRF1 could be used as a biomarker to predict the prognosis of SCLC patients and serve as a potential therapeutic target for SCLC patients.

Comprehensive analysis of transcriptomics and metabolomics revealed that the ATP-binding cassette (ABC) transporters play a central role after YAP1 knockdown in HepG2215 cells. Therefore, YAP1 knockdown inhibited HCC growth, which affected the metabolism of lipids and amino acids by regulating the expression of ALB and ABC transporters in HepG2215 cells.

METTL3 initiated the m6A modification of circKRT17, thus promoting osimertinib resistance of LUAD by enhancing YAP1 stability through EIF4A4 recruitment.

IGF2 triggers nuclear accumulation of YAP1 and upregulates YAP1 target signatures, however, these effects were abolished by either IGF1R knockdown or inhibition with PPP (picropodophyllin, an IGF1R inhibitor). Using CRC organoid and in vivo studies, we found that co-targeting IGF1R and YAP1 with PPP and VP (verteporfin, a YAP1 inhibitor) enhanced anti-tumor effects compared with PPP treatment alone...In conclusion, this study revealed a novel molecular mechanism by which CAFs promote CRC progression. The findings highlight the translational potential of the IGF2-IGF1R-YAP1 axis as a prognostic biomarker and therapeutic target for CRC.

Genetic inhibition of YAP1 using siRNA, or pharmacological inhibition of YAP1 function by the YAP1-inhibitor verteporfin, enhanced the sensitivity of KTOR71 cells to lorlatinib. These results suggest that YAP1 may mediate initial cell resistance to lorlatinib in KTOR71 cells. Thus, combinatorial therapy targeting both YAP1 and ROS1 may potentially improve the outcome of ROS1-rearranged NSCLC.

Forced expression of constitutive active YAP1 in CD44v6 knockdown cells partially restores the aggressive cancer phenotype. These important findings suggest that CD44v6 drives YAP1/TEAD signaling to enhance the CSCC cell cancer phenotype and that SFN treatment reduces CD44v6 level/function which, in turn, reduces YAP1/TEAD signaling leading to reduced stemness, EMT and tumor growth.

Overall, our data demonstrate that CAFs can activate YAP1/TEAD1 signaling and increase the secretion of NGF, therefore promoting PCa PNI. In addition, EMT induced by PNI suggests a feedback loop is present between neurons and PCa cells.

Furthermore, pharmacological inhibition of YAP1-TEAD resulted in antitumor activity in both YAP1 fusion-positive and NF2 mutant meningiomas. Together, these data indicate that disruption of the YAP1-TEAD interaction raises a potential therapeutic option for these tumors that requires future investigation.

Our studies reveal a novel mechanism and clinical significance of CXCL12/CXCR7 biased signal in promoting EMT and invasion in CRC progression. These findings highlight the potential of targeting YAP1 nuclear translocation in hampering CXCL12/CXCR7 biased signal-induced metastasis of colorectal cancer.

Overall, PAF1 cooperates with YAP1 during ADM and PC development, and verteporfin and CA3 inhibit ADM and PC cell growth by targeting the PAF1/YAP1/SOX9 axis in vitro and ex vivo models. This study identified a regulatory axis of PDAC initiation and its targeting, paving the way for developing targeted therapeutic strategies for pancreatic cancer patients.

Our findings established a novel function of APE1 in EAC progression elucidating druggable molecular vulnerabilities via targeting APE1 or YAP1 for the treatment of EAC.

Taken together, our data indicated that YAP1 knockdown/knockout reduced the SLC2A1 mediated Warburg effect by shYAP1-HepG2215 cells and Yap1 mice with liver tumors induced by DEN/TCPOBOP. DHA, as a potential YAP1 inhibitor, suppressed the SLC2A1 mediated Warburg effect in HCC.

EBV orchestrates interactions with the host and surrounding stroma by stimulating the functions of YAP1 and FAPα in fibroblasts through exosome cargos to create a more immunosuppressive, proinvasive microenvironment.

In this way, notch cannot only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, VPS25, KCNQ1OT1, KB-1460A1.5, and CKAP4 are promising prognostic indicators and a potential therapeutic targets for glioma, meanwhile, Rheb is also a potent activator of Signaling cross-talk etc. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

To determine the mechanistic roles of RASAL2 signaling and its potential as a therapeutic target in PDAC, we clarified that RASAL2 could accumulate the TIAM1 expression in different level through inhibiting YAP1 phosphorylation, increased TIAM1 mRNA expression and suppressed ubiquitination of TIAM1 protein. In conclusion, RASAL2 enhances YAP1/TIAM1 signaling and promotes PDAC development and progression.

This effect is only seen in the YAP1-activated MSTO-211H mesothelioma xenograft model, but not in the Hippo-independent HCT116 colon cancer xenograft model. Our data demonstrate that, in the context of a Hippo pathway mutated background, YAP1 activity alone is enough to maintain the growth of established tumors in vivo, thus validating the concept of inhibiting the activated YAP1-TEAD complex for the treatment of malignant pleural mesothelioma patients.

Comprehensive proteomic and drug-screening studies across pan-cancer models confirm that FAT1-mutant HNSCC exhibits selective and higher sensitivity to BRD4 inhibition by JQ1. Epigenomic analysis reveals an active chromatin state in FAT1-mutant HNSCC cells that is driven by the YAP/TAZ transcriptional complex through recruitment of BRD4 to deposit active histone marks, thereby maintaining an oncogenic transcriptional state. This study reveals a detailed cooperative mechanism between YAP1 and BRD4 in HNSCC and suggests a specific therapeutic opportunity for the treatment of this subset of head and neck cancer patients.

Targeting YAP/TAZ inhibition using the novel YAP1 inhibitor CA3 could be a promising therapeutic strategy to enhance sensitivity to sorafenib especially in HCCs with high YAP/TAZ expression in MCTS.

Overexpression of Cyr61 restored the PD-L1 and Galectin-9 expression in cells and triggered M2 polarization of macrophages, which enhanced the immune escape and maintained the proliferation and metastasis ability of PAAD cells. In conclusion, this work demonstrates that USP10 inhibits YAP1 ubiquitination and degradation to promote Cyr61 expression, which induces immune escape and promotes growth and metastasis of PAAD.

We provide data indicating the higher efficacy of CT together with YAP1 inhibitors for eradication of therapy resistant TP53 WT cancer cells. Together these results identify fetal conversion as a useful biomarker for patient prognosis and therapy prescription.