VCPIP1 facilitates pancreatic cancer progression via Hippo/YAP signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1198858 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31730554.fastq.gz | Fastqsanger.gz | |||
| SRR31730555.fastq.gz | Fastqsanger.gz | |||
| SRR31730556.fastq.gz | Fastqsanger.gz | |||
| SRR31730557.fastq.gz | Fastqsanger.gz | |||
| SRR31730558.fastq.gz | Fastqsanger.gz |
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Project description:The dys-regulation of Hippo signaling was observed in pancreatic adenocarcinoma (PAAD), while the over-activation of YAP was crucial for tumor progression. It is unclear why YAP was hyper-activated in PAAD, although the inhibitory phospho-cascade was still functional. Recently studies revealed that the ubiquitin modification of YAP also play important roles in Hippo/YAP axis and cancer progression. In order to understand the potential mechanisms of ubiquitination and deubiquitination process in YAP function, we carried out siRNA screening for critical deubiquitinases in PAAD. Via the deubiquitinases (DUB) library, we identified Valosin Containing Protein Interacting Protein 1 (VCPIP1) as an important effector in YAP function and PAAD progression. Inhibition of VCPIP1 hampered PAAD progression via Hippo signaling. Clinical data revealed that VCPIP1 was elevated in PAAD and correlated with poor survival in PAAD patients. Biochemical assays showed that VCPIP1 could interact with YAP and inhibit K48-linked poly-ubiquitination, which subsequently increased YAP stability. Interestingly, YAP could direct bind to VCPIP1 promoter region and facilitate its transcription in PAAD. Our study revealed a forward feedback loop between VCPIP1 and Hippo signaling in PAAD, indicating VCPIP1 as a potential therapeutic drug targets in PAAD.
2024-12-19 | GSE284347 | GEO
Project description:The over-activation of Hippo/YAP axis was often observed in pancreatic adenocarcinoma (PAAD), while the detailed mechanism is not totally understood. Recent studies demonstrated that the ubiquitin modification, which controlled the protein stability of YAP, played important roles in Hippo signaling and PAAD progression. In order to understand the underlying link between YAP protein stability and Hippo activity in PAAD progression, we carried out GSEA bioinformatic analysis coupled with siRNA screening and identified OTUD4 as an important effector for Hippo signaling in PAAD. OTUD4, which was highly expressed in PAAD tissue, correlated with Hippo target gene expression in PAAD tissues. Depletion of OTUD4 significantly reduced the activity of Hippo/YAP axis and hampered PAAD progression. Mechanism studies revealed that OTUD4 could interact with YAP and promote YAP K48-linked poly-ubiquitination and degradation in PAAD. In conclusion, our study identified an interesting regulation mechanism between OTUD4 and Hippo signaling in PAAD, while targeting OTUD4 could be a plausible strategy for PAAD therapy.
2025-09-21 | GSE308205 | GEO
Project description:OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis
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Project description:Colorectal cancer is one of the most lethal human malignancies in the world. Although great efforts are put in developing novel therapeutic targets, the effective targeting drugs are still limited. Recent studies reveal the abnormality of Hippo/YAP axis play critical role in the oncogenic process of Colorectal cancer. It is of great importance to demonstrate the regulation of Hippo signaling activity and YAP protein turnover in Colorectal cancer. Besides, the phosphorylation cascade on YAP function, which has been thoroughly investigated, the ubiquitination of YAP is also important in Hippo signaling status. Here, We utilized the DUB (Deubiquitinase) siRNA library to identify critical DUB for Hippo signaling. We discovered JOSD1 as a critical factor to facilitate Colorectal cancer cell stemness and progression, which deubiquitinated and stabilized YAP protein. The clinical data analysis implicated JOSD1 was correlated with YAP activity and poor survival. Molecular studies demonstrated that JOSD1 associated with the YAP protein and enhanced YAP protein stability by blocking the K48-linked polyubiquitination of YAP. Our study revealed a novel deubiquitinase of Hippo/YAP axis and one possible therapeutic target for YAP-driven Colorectal cancer
2024-09-11 | GSE256276 | GEO
Project description:Colorectal cancer progression involves dysregulated signaling pathways such as Hippo-YAP, but upstream regulators remain poorly defined. Here we demonstrate that oxysterol-binding protein-like 3 (OSBPL3) modulates Hippo-YAP signaling to drive tumor aggressiveness. Analysis of clinical specimens and experimental models showed that elevated OSBPL3 levels in colorectal cancer tissues correlate with shortened patient survival. Depleting OSBPL3 impaired cancer cell proliferation and invasion through cell cycle arrest, while its overexpression accelerated tumor growth. Mechanistic studies revealed that OSBPL3 binds 14-3-3 proteins to promote YAP1 nuclear translocation, activating downstream oncogenic pathways. Notably, tumors with high OSBPL3 expression exhibited resistance to MEK inhibitors, but this resistance was overcome by YAP1 suppression or combined YAP/MEK inhibition in patient-derived organoids. These results establish OSBPL3 as a critical Hippo-YAP pathway regulator and propose targeting OSBPL3-mediated signaling as a therapeutic strategy for colorectal cancers with Hippo pathway alterations
2025-09-30 | GSE308083 | GEO
Project description:Triple negative breast cancer (TNBC) is one of the most lethal breast cancer subtypes. Due to a lack of effective therapeutic targets, chemotherapy is still the main medical treatment for TNBC patients. Thus, it is important and necessary to identify novel therapeutic targets for TNBC. Recent genomic studies implicated the hyper-activation of Hippo/YAP signaling in TNBC, manifesting its critical roles in TNBC carcinogenesis and cancer progression. RBCK1 was firstly identified as an important component for linear ubiquitin assembly complex (LUBAC) and facilitates NFKB signaling in immune response. Further studies showed RBCK1 also facilitated luminal type breast cancer growth and endocrine resistance via trans-activation estrogen receptor alpha. Interestingly, our data revealed an opposite function for RBCK1 in TNBC progression. RBCK1 over-expression inhibited TNBC cell progression in vitro and in vivo, while RBCK1depletion promoted TNBC cell invasion. The whole genomic expression profiling showed that RBCK1 depletion activated Hippo/YAP axis. RBCK1 depletion increased YAP protein level and Hippo target gene expression in TNBC. The molecular biology studies showed that RBCK1 could associate with YAP protein and enhance YAP protein stability via promoting YAP K48-linked poly-ubiquitination at several YAP lysine sites (K76, K204 and K321). Our study revealed the multi-faced RBCK1 function in different subtypes of breast cancer patients and a promising therapeutic target for TNBC treatment.
2022-02-05 | GSE195712 | GEO
Project description:JOSD1 facilitates colorectal cancer progression via stabilizing YAP
| PRJNA1078851 | ENA
Project description:ZDHHC15 mediates Hippo/YAP pathway palmitoylation and regulates tumor progression
| PRJNA985614 | ENA
Project description:The Post-translational modification of Hippo/YAP pathway members plays an important role in regulating the activation of Hippo/YAP pathway and its effects in tumors. S-Palmitoylation, also known as S-acylation, is the most common protein Lipid modification, mainly composed of palmitoyl transferases (PATs) from the DHHC (Asp His His Cys) family Catalysis. The results showed that ZDHHC15 mediated palmitoylation of KIBRA up-regulated the expression of YAP downstream target genes, and regulated the invasion function of breast cancer and ovarian cancer cells. The research results will reveal new regulatory mechanisms of the Hippo pathway
2024-12-17 | GSE235258 | GEO
Project description:Splicing dysregulations extensively occur in cancers, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signaling, a key pathway that regulates cell proliferation and organ size, is under control of a new splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signaling, undergoes alternative splicing facilitated by the tumor suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks N-terminal DNA-binding domain but maintains YAP-interaction domain. TEAD4-S is located in both nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumor growth in xenograft mouse model. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether these data reveal a novel RBM4-mediated splicing switch that serves to fine-tune Hippo-YAP pathway. Cell lines stably expressing YAP, YAP/TEAD4-S, YAP/TEAD4-FL, YAP/RBM4 and control vector were created, and the total RNA was purified from the cells using TRIzol reagents. The polyadenylated RNAs were purified for construction of sequencing library using kapa TruSeq Total RNA Sample Prep kits (UNC High Throughput Sequencing Facility).
2016-06-16 | E-GEOD-80372 | biostudies-arrayexpress