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Status |
Public on Jan 31, 2008 |
Title |
Identification of YAP target genes in MCF10A cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT). We used microarrays to detail the global program of gene expression to identify YAP target genes.
PUBLICATION ABSTRACT: The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Since this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition (EMT), suggesting that this is a key feature of YAP signaling in mammalian cells. Keywords: vector vs. YAP comparison
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Overall design |
MCF10A cells were infected with retrovirus constructs (vector or YAP) and puromycin was used to select for transduced cells. Cells were split and grown to ~60-75%% confluency at which point they were harvested for RNA. Vector vs. YAP comparison was done in duplicate.
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Contributor(s) |
Smolen GA, Haber DA, Zhang J |
Citation(s) |
18413746 |
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Submission date |
Jan 17, 2008 |
Last update date |
Mar 25, 2019 |
Contact name |
Daniel Haber |
Organization name |
Massachusetts General Hospital
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Department |
Cancer Center
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Street address |
Rm.7119, Bldg.149, 13th Street
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City |
Charlestown |
State/province |
MA |
ZIP/Postal code |
02129 |
Country |
USA |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (4)
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GSM257525 |
vector control cells, biological rep1 |
GSM257526 |
YAP-overexpressing cells, biological rep1 |
GSM257527 |
vector control cells, biological rep2 |
GSM257528 |
YAP-overexpressing cells, biological rep2 |
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Relations |
BioProject |
PRJNA108311 |
Supplementary file |
Size |
Download |
File type/resource |
GSE10196_RAW.tar |
22.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
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