PXD038305

PXD038305 is an original dataset announced via ProteomeXchange.

Title	PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer
Description	Dysregulation of the PI3K/AKT pathway is a common occurrence in ovarian carcinomas. Loss of the tumour suppressor PTEN in high-grade serous ovarian carcinoma (HGSOC) is associated with a patient subgroup with poor prognosis. The cellular mechanisms of how PTEN loss contributes to HGSOC are largely unknown. We utilise long-term time-lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype of PTEN loss. PTEN deficiency does not affect proliferation but rather induces PI(3,4,5)P3-rich and -dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability upon PTEN loss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase-activating protein (GAP) AGAP1 and the ECM receptor β1-integrin as key ARF6 interactors regulating the PTEN loss-associated invasion phenotype. ARF6 functions to promote invasion by controlling the recycling of internalised, active β1-integrin complexes to maintain invasive activity into the ECM. The expression of the ARF6-centred complex in HGSOC patients is inversely associated with outcome, allowing identification of patient groups with improved versus poor outcome. ARF6 may represent a new therapeutic vulnerability in PTEN-depleted HGSOC tumours.
HostingRepository	PRIDE
AnnounceDate	2023-07-11
AnnouncementXML	Submission_2023-07-11_08:08:43.532.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038305
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	SergioLilla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-23 02:01:23	ID requested
⏵ 1	2023-07-11 08:08:43	announced

10.6019/PXD038305;

submitter keyword: HGSOC, ARF6, ID8, PI3K/AKT pathway, GTPase, TurboID

Sara RossanaZanivan
contact affiliation	CRUK - Beatson Institute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom
contact email	s.zanivan@beatson.gla.ac.uk
lab head
SergioLilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038305
     1. Label: PRIDE project
     2. Name: PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer