PXD053682

PXD053682 is an original dataset announced via ProteomeXchange.

Title	CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds
Description	FOXL2 is a transcription factor that plays a key role in sex determination, ovary development and maintenance. Mutations related to this gene have been described in syndromes involving premature ovarian failure and granulosa cell tumors. This kind of rare cancer (less than 5% of diagnosed ovarian cancers) has been causally associated with the FOXL2 c.402C>G, p.C134W mutation in 97% of the adult cases (AGCTs). In this study, we have used CRISPR technology to specifically eliminate the FOXL2 c.402C>G mutation in granulosa tumor cells. Our results indicate that this Cas9-mediated strategy allows the specific elimination of the mutation with no activity on the wild type allele. Granulosa cells depleted on FOXL2 c.402C>G show a reduced malignant phenotype. Specifically, we detect changes in cell proliferation, invasion, and cell death levels. In addition, we show that granulosa tumor cells become more susceptible to Dasatinib and Ketoconazole treatments when FOXL2 c.402C>G allele is eliminated. Our transcriptomic and proteomic analyses indicate that CRISPR-modified granulosa tumor cells significantly change their expression signature towards a wild type like phenotype. Finally, this expression signature has led us to discover new compounds with antiproliferative and proapoptotic effects on granulosa cell tumor cells. Our results demonstrate the potential of CRISPR for specifically targeting and eliminating a granulosa cell tumor-causing mutation, as well as its therapeutic potential for the treatment of this rare ovarian cancer.
HostingRepository	PRIDE
AnnounceDate	2025-03-15
AnnouncementXML	Submission_2025-03-15_13:41:52.670.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ana Montero Calle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; carbamoylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-05 02:42:48	ID requested
⏵ 1	2025-03-15 13:41:53	announced

10.1002/1878-0261.13799;

submitter keyword: TMT, Rare cancer, CRISPR,Granulosa cell tumor, Proteomics, FOXL2

Ignacio Pérez de Castro Insua
contact affiliation	Instituto de Investigación de Enfermedades Raras; Instituto de Salud Carlos III; Ctra. Majadahonda-Pozuelo km2.2; E-28029 Madrid, Spain
contact email	iperez@isciii.es
lab head
Ana Montero Calle
contact affiliation	Instituto de Salud Carlos III
contact email	ana.monteroc@isciii.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053682
     1. Label: PRIDE project
     2. Name: CRISPR targeting of FOXL2 c.402C>G mutation reduces malignant phenotype in granulosa tumor cells and identifies anti-tumoral compounds