Gomisin G inhibits pancreatic cancer cell growth through the Hippo-YAP signaling pathway
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ABSTRACT:
PROVIDER: PRJNA1127671 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29525272_1.fastq.gz | Fastqsanger.gz | |||
| SRR29525272_2.fastq.gz | Fastqsanger.gz | |||
| SRR29525273_1.fastq.gz | Fastqsanger.gz | |||
| SRR29525273_2.fastq.gz | Fastqsanger.gz | |||
| SRR29525274_1.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: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
Project description:VCPIP1 facilitates pancreatic cancer progression via Hippo/YAP signaling
| PRJNA1198858 | ENA
Project description:Purpose: The purpose of this study was to investigate the effect of Gomisin G on the transcription level of pancreatic cancer cells SW1990.
2024-06-29 | GSE270676 | GEO
Project description:As a classic tumor suppressor pathway, Hippo signaling axis is activated by various extra-pathway factors to regulate cell differentiation and organ development. However, recent studies have reported that the activation of Hippo signaling pathway may be more dependent on the autophosphorylation of its core kinase cassette. Here, we demonstrate that protein arginine methyltransferase 5 (PRMT5) is involved in inducing the inactivation of Hippo signaling pathway in pancreatic cancer. Our study shows that the initiator serine/threonine kinase 3 (STK3, also known as MST2) of Hippo signaling pathway can be symmetrically di-methylated at arginine-461 (R461) and arginine-467 (R467) in the SARAH domain by PRMT5, and the methylated MST2 suppresses its autophosphorylation and kinase activity by blocking the formation of homodimer, thereby inactivating Hippo signaling pathway in pancreatic cancer. Moreover, we also discover that the specific PRMT5 inhibitor GSK3326595 re-activates the dysregulated Hippo signaling pathway and inhibits the growth of human-derived pancreatic cancer xenografts in immunodeficient mice, which provides a theoretical foundation for the clinical application of PRMT5 inhibitor in pancreatic cancer.
2023-11-17 | GSE241402 | GEO
Project description:The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors YAP and TAZ are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences which suggest there may be differences in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, we generated knockout cells and evaluated them in response to many conditions and stimuli. Here, we used RNA-seq to identify and compare differences in the transcriptional profiles between the YAP and TAZ.
2018-05-25 | GSE111583 | GEO
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:The prevalent understanding of Hippo signaling is one inhibitory pathway in tumor growth via deactivating the potential of YAP-TEAD transcriptional complex. The aberrant activation of YAP was observed in a series of human malignancies. However, recent studies implicate that in certain cancer types, YAP could be a tumor suppressor. Here, we reported a context-dependent function of YAP in clear cell renal carcinoma (ccRCC). Inhibition of Hippo kinase activity impeded ccRCC tumor growth and NF-κB transcriptional programs. Pharmacological blocking Hippo kinase activity or ectopic activation of YAP suppressed tumor growth in xenograft and PDX models. Mechanism studies revealed that TEAD could synchronize with P65 for NF-κB signaling activation, while YAP disrupted TEAD-NF-κB interactions and dissociated P65 from its target gene promoter, thereby inhibiting NF-κB transcriptional programs and ccRCC tumor growth. Our study identified a novel crosstalk between Hippo and NF-κB pathway, uncovered a non-canonical regulation of Hippo/YAP axis in renal cancer and suggested a novel strategy to ccRCC treatments by YAP activation.
2024-05-31 | GSE252142 | GEO
Project description:The prevalent understanding of Hippo signaling is one inhibitory pathway in tumor growth via deactivating the potential of YAP-TEAD transcriptional complex. The aberrant activation of YAP was observed in a series of human malignancies. However, recent studies implicate that in certain cancer types, YAP could be a tumor suppressor. Here, we reported a context-dependent function of YAP in clear cell renal carcinoma (ccRCC). Inhibition of Hippo kinase activity impeded ccRCC tumor growth and NF-κB transcriptional programs. Pharmacological blocking Hippo kinase activity or ectopic activation of YAP suppressed tumor growth in xenograft and PDX models. Mechanism studies revealed that TEAD could synchronize with P65 for NF-κB signaling activation, while YAP disrupted TEAD-NF-κB interactions and dissociated P65 from its target gene promoter, thereby inhibiting NF-κB transcriptional programs and ccRCC tumor growth. Our study identified a novel crosstalk between Hippo and NF-κB pathway, uncovered a non-canonical regulation of Hippo/YAP axis in renal cancer and suggested a novel strategy to ccRCC treatments by YAP activation.
2023-12-31 | GSE235788 | GEO
Project description:It has been shown that up regulation activity of CD81(TAPA-1, the portal of entry of Hepatitis C virus) by agonistic antibody results in phosphorylation of Ezrin. We have previously shown that in liver, Ezrin phosphorylation occurs via Syk kinase, causing suppression of hippo intensity, therefore increases sequential Yap activity. The opposite occurs when Glypican-3 (GPC3) or E2 protein of HCV bind to CD81. Mice over-expressing GPC3 in hepatocytes have decreased p-Ezrin(Thr567) and Yap, increased Hippo activity and suppressed liver regeneration. The role of Ezrin in these processes has been speculated, but not proven. We now provide dynamic picture of Ezrin regulates Hippo pathway and Yap. Forced expression of plasmids expressing mutant Ezrin (T567D) (which mimics p-Ezrin(Thr567)) suppressed Hippo activity and activated Yap signaling. And this mutant Ezrin drive more cell proliferation to cell division through up regulated Yap activity in vitro and in vivo. CD81 loses expression, while p-Ezrin(Thr567) increases in JM1 and JM2 hepatocellular carcinoma (HCC) cells. Administration with compound NSC668394, a characterized p-Ezrin(Thr567) antagonist, caused significant decrease in HCC cell proliferation. We additionally present evidence that pEzrin(T567) is also controlled by EGFR and MET. Conclusions: Ezrin phosphorylation, mediated by CD81 associated Syk kinase, is directly involved in regulation of Hippo pathway, Yap levels and growth rates of normal and neoplastic hepatocytes. The finding has mechanistic and potentially therapeutic applications in understanding and regulating growth of hepatocytes and HCC and HCV pathogenesis. We used microarrays to detail the global programme of gene expression in GFP positive hepatocytes of FVB mice adminstration with EzrinT567D plasmids
2020-03-27 | GSE145572 | GEO