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Series GSE158500 Query DataSets for GSE158500
Status Public on Dec 04, 2020
Title Fat1 deletion promotes hybrid EMT state with enhanced tumor progression, stemness, and metastasis (ATAC-Seq)
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary FAT1, a protocadherin, is among the most frequently mutated genes in human cancers. However, the role and the molecular mechanisms by which FAT1 mutations control tumor initiation and progression are poorly understood. Here, using different mouse cancer models including skin squamous cell carcinoma (SCC) and lung tumors we found that Fat1 deletion accelerated tumor initiation and malignant progression and promoted hybrid epithelial to mesenchymal transition (EMT) phenotype. This hybrid EMT state was also found in FAT1 mutated human SCCs. Fat1 deleted skin SCCs presented increased tumor stemness and spontaneous metastasis. Transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies revealed that FAT1 loss of function activates a CAMK2/CD44/SRC axis that promotes YAP/ZEB1 nuclear translocation and stimulates the mesenchymal state, as well as a CAMK2-EZH2 axis that promotes activation of SOX2, which sustains the epithelial state. This comprehensive analysis also identified drug resistance and vulnerabilities in FAT1 deficient tumors with important implications for cancer therapy. Altogether, our studies revealed that Fat1 loss of function promotes tumor initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.
 
Overall design FACS isolated Epcam+ and Epcam- tumor cells from DMBA/TPA K14Cre;RYFP and K14Cre;Fat1fl/fl;RYFP skin SCCs.
 
Contributor(s) Pastushenko I, Mauri F, Song Y, Blanpain C
Citation(s) 33328637
Submission date Sep 24, 2020
Last update date Mar 05, 2021
Contact name Yura Song
E-mail(s) yura.song@ulb.be
Organization name Université Libre de Bruxelles
Lab Laboratory of Stem Cells and Cancer
Street address 808, route de Lennik
City Bruxelles
ZIP/Postal code 1070
Country Belgium
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (3)
GSM4801777 RYFPIIcar2YFP-Epp
GSM4801778 F3E13-14-FatKO-Epp
GSM4801779 F3E13-14-FatKO-Epm
This SubSeries is part of SuperSeries:
GSE158506 Fat1 deletion promotes hybrid EMT state with enhanced tumor progression, stemness, and metastasis
Relations
BioProject PRJNA665480
SRA SRP285247

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE158500_RAW.tar 1.2 Gb (http)(custom) TAR (of BEDGRAPH)
GSE158500_rawcount_ATAC_mouse.txt.gz 1.5 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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