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Series GSE188463 Query DataSets for GSE188463
Status Public on Nov 11, 2021
Title Hierarchy of TGFβ/SMAD, Hippo/YAP/TAZ and Wnt/β-catenin signaling in melanoma phenotype switching
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary In melanoma, a switch from a proliferative melanocytic to an invasive mesenchymal phenotype is based on dramatic transcriptional reprogramming which involves complex interactions between a variety of signaling pathways and their downstream transcriptional regulators. TGFb/SMAD, Hippo/YAP/TAZ and Wnt/b-catenin signaling pathways are major inducers of transcriptional reprogramming and converge at several levels. Here, we report that TGFb/SMAD, YAP/TAZ and b-catenin are all required for a proliferative-to-invasive phenotype switch. Loss and gain of function experimentation, global gene expression analysis, and computational nested effects models revealed the hierarchy between these signaling pathways and identified shared target genes. SMAD-mediated transcription at the top of the hierarchy leads to the activation of YAP/TAZ and of b-catenin, with YAP/TAZ governing an essential sub-program of TGFb-induced phenotype switching. Wnt/b-catenin signaling is situated further downstream and exerts a dual role: it promotes the proliferative, differentiated melanoma cell phenotype and it is essential but not sufficient for SMAD or YAP/TAZ-induced phenotype switching. The results identify epistatic interactions among the signaling pathways underlying melanoma phenotype switching and highlight the priorities in targets for melanoma therapy.
 
Overall design Stimulation of two melanoma cell lines with TGFb1 and Wnt-3a, and siRNA knock-downs of LATS1/2 in all possible combinations including two controls (total 9 samples per cell line). Technical duplicates were sequenced.
 
Contributor(s) Lüönd F, Pirkl M, Kalathur RK, Beerenwinkel N, Hisano M, Prestigiacomo V, Christofori G, Beisel C
Citation(s) 34819356
Submission date Nov 09, 2021
Last update date Feb 10, 2022
Contact name Gerhard Christofori
Organization name University of Basel
Department Department of Biomedicine
Lab Christofori Lab
Street address Mattenstrasse 28
City Basel
ZIP/Postal code 4058
Country Switzerland
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (36)
GSM5683339 Vehicle Control M0009 R1 [M0009_Vehicle_Control_1]
GSM5683340 Vehicle Control M0009 R2 [M0009_Vehicle_Control_2]
GSM5683341 siCtrl TGFb1 M0009 R1 [M0009_siCtrl_TGFb1_1]
Relations
BioProject PRJNA778984
SRA SRP345234

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Supplementary file Size Download File type/resource
GSE188463_counts_quasR_oposite_rawdata.txt.gz 1.2 Mb (ftp)(http) TXT
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