PXD008100

PXD008100 is an original dataset announced via ProteomeXchange.

Title	SILAC identifies LAD1 as an oncogenic filamin binder regulating actin dynamics in response to EGF and marking aggressive breast tumors
Description	Mutations mimicking growth factor-induced proliferation and motility characterize aggressive subtypes of mammary tumors. To unravel novel players, we applied phosphoproteomics on untransformed mammary cells, which were pre-stimulated with the epidermal growth factor (EGF). This analysis identified ladinin-1 (LAD1), a hitherto poorly characterized protein, as a phosphor-effector of the EGF-to-ERK pathway. We report that LAD1 is essential for mammary cell proliferation and migration. LAD1 is transcriptionally induced, undergoes phosphorylation by EGF and partly co-localizes with actin stress fibers. Yeast 2-hybrids, proximity ligation and co-immunoprecipitation assays revealed that LAD1 binds with filamins, actin cross-linking proteins. Co-sedimentation analyses attribute to LAD1 a role in actin treadmilling, probably in collaboration with SFN/14-3-3sigma. Depletion of LAD1 led to a decrease in transcripts relevant to cell survival, and inhibited growth of mammary xenografts in an animal model. Furthermore, LAD1 is highly expressed in two aggressive subtypes of breast cancer, as well as predicts poor patient prognosis. This study identifies a new cytoskeletal component essential for cell migration and for the acquisition of oncogenic attributes by human mammary tumors.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:41:37.408.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-01 03:40:09	ID requested
1	2019-11-19 12:22:19	announced
⏵ 2	2024-10-22 04:41:39	announced	2024-10-22: Updated project metadata.

Roth L, Srivastava S, Lindzen M, Sas-Chen A, Sheffer M, Lauriola M, Enuka Y, Noronha A, Mancini M, Lavi S, Tarcic G, Pines G, Nevo N, Heyman O, Ziv T, Rueda OM, Gnocchi D, Pikarsky E, Admon A, Caldas C, Yarden Y, SILAC identifies LAD1 as a filamin-binding regulator of actin dynamics in response to EGF and a marker of aggressive breast tumors. Sci Signal, 11(515):(2018) [pubmed]

10.1126/scisignal.aan0949;

curator keyword: Biomedical

submitter keyword: LAD1 EGF phosphoproteome

Yosef Yarden
contact affiliation	Departments of Biological Regulation , Weizmann Institute of Science, Rehovot , Israel
contact email	yosef.yarden@weizmann.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@tx.technion.ac.il
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/2019/11/PXD008100

PRIDE project URI

• PRIDE
  1. PXD008100
     1. Label: PRIDE project
     2. Name: SILAC identifies LAD1 as an oncogenic filamin binder regulating actin dynamics in response to EGF and marking aggressive breast tumors