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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 01, 2012 |
| Title |
YAP Inhibition in HCC cells (Hep3B) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA.
Loss of contact inhibition and anchorage-independent growth are hallmarks of cancer cells. In this context, frequent inactivation of the Hippo pathway and subsequent nuclear enrichment of the transcriptional coactivator yes-associated protein (YAP) uncouple cell proliferation and anti-apoptosis from contact inhibition, associated with uncontrolled tumor growth and tumor cell dissemination. However, general molecular mechanisms of tumor-supporting YAP activity remain unclear. In this study, we show that overexpression and nuclear accumulation of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells leads to an induction of the Notch pathways through transcriptional activation of the Notch ligand jagged-1 (Jag-1). This induction of Jag-1 strictly depends on binding of YAP to TEAD4 and does not rely on WNT/β-catenin pathway activity. Co-activation of YAP, TEAD4, Jag-1, and the Notch target gene Hes-1 was significantly higher in HCC from patients with poor prognosis. High-level expression and nuclear accumulation of YAP correlates with Jag-1/Notch activation not only in human HCC tissues, but also in colon and pancreatic cancer tissues. Thus, our data demonstrate that YAP-driven co-activation of the Jag-1/Notch pathway in part facilitates oncogenic properties of the oncogene YAP not only in HCC but also in different gastrointestinal malignancies.
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| Overall design |
Expression profiling of untreated HCC cell lines (control 1), cells transfected with scrambled/nonsense siRNA (control 2), and after siRNA-mediated YAP inhibition.
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| Contributor(s) |
Tschaharganeh DF, Chen X, Latzko P, Malz M, Gaida M, Felix K, Singer S, Pinna F, Gretz N, Sticht C, Delogu S, Evert M, Biao F, Ribback S, Jiang L, Brozzetti S, Bergmann F, Dombrowski F, Schirmacher P, Calvisi D, Breuhahn K |
| Citation(s) |
23419361 |
| Submission date |
Jan 11, 2012 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Carsten Sticht |
| Organization name |
University Heidelberg
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| Department |
ZMF
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| Street address |
Theodor-Kutzer-Ufer
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| City |
Mannheim |
| ZIP/Postal code |
68169 |
| Country |
Germany |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA151075 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35004_RAW.tar |
35.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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