PXD022268-1
PXD022268 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Fat1 deletion promotes hybrid EMT state, tumor stemness, and metastasis |
Description | FAT1, a protocadherin, is among the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. In the present study we used different mouse cancer models including skin squamous cell carcinoma (SCC) and lung tumours we found that Fat1 deletion accelerated tumour 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 tumour stemness and spontaneous metastasis. Transcriptional and chromatin profiling revealed that Yap1 and Sox2 are involved in promoting and stabilizing hybrid EMT state. To unravel the molecular mechanisms by which FAT1 (a protein located on the plasma membrane), lead to the transcriptional changes, we performed phosphor-proteomic analysis of A388 FAT1 WT human SCC cell lines and A388 FAR1 CRISPR KO. This analysis 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 tumours with important implications for cancer therapy. Altogether, our studies revealed that Fat1 loss of function promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state. |
HostingRepository | PRIDE |
AnnounceDate | 2021-03-04 |
AnnouncementXML | Submission_2021-03-04_13:37:57.149.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Delphi Van Haver |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2020-10-30 04:15:13 | ID requested | |
⏵ 1 | 2021-03-04 13:37:57 | announced |
Publication List
Pastushenko I, Mauri F, Song Y, de Cock F, Meeusen B, Swedlund B, Impens F, Van Haver D, Opitz M, Thery M, Bareche Y, Lapouge G, Vermeersch M, Van Eycke YR, Balsat C, Decaestecker C, Sokolow Y, Hassid S, Perez-Bustillo A, Agreda-Moreno B, Rios-Buceta L, Jaen P, Redondo P, Sieira-Gil R, Millan-Cayetano JF, Sanmatrtin O, D'Haene N, Moers V, Rozzi M, Blondeau J, Lemaire S, Scozzaro S, Janssens V, De Troya M, Dubois C, P, é, rez-Morga D, Salmon I, Sotiriou C, Helmbacher F, Blanpain C, Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis. Nature, 589(7842):448-455(2021) [pubmed] |
Keyword List
submitter keyword: Hybrid EMT, FAT1, metastasis, stemness |
Contact List
Cedric Blanpain | |
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contact affiliation | Stem Cell and Developmental Biology, Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Bruxelles, Belgium |
contact email | cedric.blanpain@ulb.ac.be |
lab head | |
Delphi Van Haver | |
contact affiliation | VIB Proteomics Core |
contact email | delphi.vanhaver@vib-ugent.be |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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