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| Status |
Public on May 31, 2024 |
| Title |
YAP targets TEAD4-NF-κB complex and inhibits ccRCC tumor growth |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Chromatin Immunoprecipitation DNA-sequencing of p65 and TEAD using siTEAD and XMU-MP-1 treatment in 786-O cells
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| Contributor(s) |
Li Z, YU M, Zhu J |
| Citation missing |
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| Submission date |
Dec 27, 2023 |
| Last update date |
May 31, 2024 |
| Contact name |
Tianwei Jia |
| E-mail(s) |
202115615@mail.sdu.edu.cn
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| Organization name |
Shandong university
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| Street address |
天桥区
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| City |
Jinan |
| State/province |
Shandong |
| ZIP/Postal code |
250000 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| GSM7995074 |
786-O,p65_siTEAD4,ChIP |
| GSM7995075 |
786-O,Input_Veh,ChIP |
| GSM7995076 |
786-O,p65_Veh,ChIP |
| GSM7995077 |
786-O,Input_XMU,ChIP |
| GSM7995079 |
786-O,p65_XMU,ChIP |
| GSM7995082 |
786-O,TEAD_XMU,ChIP |
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| Relations |
| BioProject |
PRJNA1057865 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE252142_RAW.tar |
2.7 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
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