Amplification of Hippo Signaling Pathway Genes Is Governed and Implicated in the Serous Subtype-Specific Ovarian Carcino-Genesis

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1781 - 1781

Published: May 5, 2024

Among women, ovarian cancer ranks as the fifth most common cause of cancer-related deaths. This study examined impact Hippo signaling pathway on carcinogenesis. Therefore, signatures related to were derived from molecular database (MSigDB) and used for further analysis. The Z score-based activation scoring method was employed investigate expression patterns these in mRNA profiles cohorts. Compared other subtype tumors, results this show that are dysregulated prominently serous subtype-specific A receiver operating characteristic (ROC) curve-based gene set, yes-associated protein 1 (YAP1), mammalian sterile 20-like kinases (MST1) genes can predict tumors by higher specificity sensitivity with significant areas under curve values also reconfirmed dysregulations. Moreover, sets studied mutation analysis profile high-grade adenocarcinoma cBioPortal database. OncoPrint reveal amplified highly during grade three stage third or fourth type tumors. In addition, Dependency Map (DepMap) plot clearly significantly across cell lines. Finally, overall survival (OS) investigations revealed expressions poor linked expressed conditions subtypes patients p-values (p < 0.05). Thus, current finding would help develop targeted therapies treatment

Language: Английский

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Targeting the Hippo pathway in cancer: kidney toxicity as a class effect of TEAD inhibitors?

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Targeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217467 - 217467

Published: Jan. 1, 2025

Language: Английский

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Transient activation of YAP/TAZ confers resistance to morusin-induced apoptosis

BMC Molecular and Cell Biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 20, 2025

The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation cell growth, tissue homeostasis, apoptosis. Morusin, compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple pathways, including PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, apoptosis pathways. This study explores effects morusin on activation its implications for resistance. Our investigation revealed induces transient activation, characterized dephosphorylation at S127 nuclear localization, followed gradual rephosphorylation cells. Notably, this occurs independently canonical LATS1/2, MINK1, MAPK pathways during inactivation stage. Furthermore, morusin-induced stress granule formation was significantly impaired YAP/TAZ-depleted cells, suggesting role Additionally, expression constitutively active MINK1 maintained reduced apoptosis, indicating prolonged can enhance resistance death. These findings suggest YAP/TAZ are crucial could anti-cancer efficacy morusin. provides new insights into molecular mechanisms morusin, highlighting therapeutic strategies against disrupting

Language: Английский

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USP43 drives cervical carcinoma progression through regulation of the Hippo/TAZ pathway

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114217 - 114217

Published: Feb. 7, 2025

Language: Английский

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Targeting the Hippo- Yes-Associated Protein/Transcriptional Coactivator with PDZ-Binding Motif Signaling Pathway in Primary Liver Cancer Therapy

Onco, Journal Year: 2024, Volume and Issue: 4(3), P. 217 - 231

Published: Aug. 22, 2024

Liver cancer imposes a pervasive global health challenge, ranking among the most prevalent cancers worldwide. Its prevalence and mortality rates are on concerning upward trajectory exacerbated by dearth of efficacious treatment options. The Hippo signaling pathway, originally discovered in Drosophila, comprises following four core components: MST1/2, WW45, MOB1A/B, LATS1/2. This pathway regulates cellular localization transcriptional coactivator Yes-associated protein/transcriptional with PDZ-binding motif (YAP/TAZ) through series enzymatic reactions. Hippo-YAP/TAZ maintains balance between cell proliferation apoptosis, tissue organ sizes, stabilizes internal environment. Abnormalities any genes within such as deletion or mutation, disturb delicate creating favorable condition for tumor initiation progression. Mutations epigenetic alterations components can lead to its inactivation. Consequently, YAP/TAZ becomes overexpressed activated, promoting excessive inhibiting apoptosis. dysregulation is closely associated development liver cancer. review discusses pivotal role pathogenesis progression By elucidating mechanisms, we aim offer new insights into potential therapeutic targets effectively combating

Language: Английский

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Targeting the Hippo-YAP/TAZ Signaling Pathway in Primary Liver Cancer Therapy

Published: July 23, 2024

Liver cancer imposes a pervasive global health challenge, ranking among the most prevalent cancers worldwide. Its prevalence and mortality rates are on concerning upward trajectory exacerbated by dearth efficacious treatment options. The Hippo signaling pathway, originally discovered in Drosophila, comprises four core components: MST1/2, WW45, MOB1A/B, LATS1/2. This pathway regulates cellular localization of transcriptional coactivator YAP/TAZ (Yes-associated protein/PDZ-binding motif) through series enzymatic reactions. Hippo/YAP/TAZZ maintains balance between cell proliferation apoptosis, regu-lates tissue organ sizes, stabilizes internal environment. Abnormalities any genes within such as deletion or mutation, disturb delicate creating favorable condition for tumor initiation progression. Mutations epigenetic alterations components can lead to its inactivation. Consequently, becomes overexpressed activated, promoting excessive inhibiting apoptosis. dysregulation is closely associated with development liver cancer. review discusses pivotal role pathogenesis progression By elucidating mechanisms, we aim offer new insights into potential therapeutic targets effectively combating

Language: Английский

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Gastric Adenocarcinomas with CDX2 Induction Show Higher Frequency of TP53 and KMT2B Mutations and MYC Amplifications but Similar Survival Compared with Cancers with No CDX2 Induction

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(24), P. 7635 - 7635

Published: Dec. 15, 2024

Background: Gastric cancer is one of the most prevalent gastrointestinal cancers. Mortality high, and improved treatments are needed. A better understanding pathophysiology disease discovery biomarkers for targeted therapies paramount therapeutic progress. CDX2, a transcription factor hindgut specification, induced in several gastric cancers, especially with intestinal differentiation, could be helpful defining sub-types particular characteristics. Methods: cancers CDX2 mRNA expression were identified from cohort The Cancer Genome Atlas (TCGA) compared that had no induction. Induced was defined as z-score relative to all samples above 0, non-induced below -1. Results: Patients induction older, less frequently diffuse histology, more often mutations TP53 KMT2B amplifications MYC. correlated HNF4α reversely SOX2. showed lower PD-L1 than but did not differ CLDN18 expression. Progression-free overall survival two groups also significantly different. Conclusion: displayed specific characteristics differentiate them interest optimizing current future therapies.

Language: Английский

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Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Meningiomas are the most common primary brain tumors in adults. Although generally benign, a subset of meningiomas is higher grade, shows aggressive growth behavior and recurs even after multiple surgeries. Around half all harbor inactivating mutations NF2. While benign low-grade NF2 mutant exhibit few genetic events addition to inactivation, high-grade frequently highly aberrant genome. We others have previously shown that inactivation leads YAP1 activation acts as pivotal oncogenic driver meningiomas. Using bulk single-cell RNA-Seq data from large cohort human meningiomas, we show decreased levels activity compared their counterparts. Decreased expression YAP target genes significantly associated with an increased risk recurrence. then identify competitor VGLL4 well upstream regulators FAT3/4 potential mechanism for downregulation High these In vitro, overexpression resulted meningioma cells, confirming direct link between observed Our results shed new insight on biology may important implications efficacy therapies targeting

Language: Английский

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Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4

Neuro-Oncology Advances, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

Meningiomas are the most common primary central nervous system tumors in adults. Although generally benign, a subset is of higher grade and ultimately fatal. Around half all meningiomas harbor inactivating mutations NF2, leading to deregulation oncogenic YAP1 activity. While benign NF2 mutant exhibit few genetic events addition inactivation, aggressive high-grade frequently highly aberrant genome. It unclear if different grades equally reliant on YAP

Language: Английский

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