PXD037401

PXD037401 is an original dataset announced via ProteomeXchange.

Title	LncRNA LETS1 promotes TGF--induced EMT and cancer progression
Description	Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:59:20.959.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-13 15:31:05	ID requested
1	2023-07-31 09:29:27	announced
2	2023-11-14 06:50:28	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:59:21	announced	2024-10-22: Updated project metadata.

10.1126/SCISIGNAL.ADF1947;

submitter keyword: lncRNA

TFG-beta

Cancer

EMT

Román González-Prieto
contact affiliation	Genome Proteomics Laboratory, CABIMER-US, Seville, Spain
contact email	roman.gonzalez@cabimer.es
lab head
Román González-Prieto
contact affiliation	Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact email	roman.gonzalez@cabimer.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD037401

PRIDE project URI

• PRIDE
  1. PXD037401
     1. Label: PRIDE project
     2. Name: LncRNA LETS1 promotes TGF--induced EMT and cancer progression