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PXD032693-1

PXD032693 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting LIPA Independent of its Lipase Activity is a Therapeutic Strategy in Solid Tumors via Induction of Endoplasmic Reticulum Stress
DescriptionTriple negative breast cancers (TNBC) are associated with poor clinical outcomes due to a lack of targeted therapies. Here, we identified a small molecule ERX-41 with potent activity against TNBC cell lines, primary tumor explants and xenografts. ERX-41 induced endoplasmic reticulum (ER) stress and caused cell death. We identified lysosomal acid lipase A (LIPA) gene as the molecular target for ERX-41 and critical for ERX-41 to induce ER stress and cell death. Mechanistically, interaction of ERX-41 with LIPA alters expression of multiple ER-resident proteins involved in protein folding. Importantly, we defined that ER localization of LIPA but not its lipase function are necessary for ERX-41 activity in TNBC. Our study implicates a new targeted strategy for multiple solid tumors, including breast, brain, pancreatic and ovarian, whereby a small orally bioavailable molecule (ERX-41) targeting LIPA blocks protein folding, induces ER stress and causes cell death.
HostingRepositoryMassIVE
AnnounceDate2022-03-28
AnnouncementXMLSubmission_2022-03-28_22:30:49.684.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSusan T. Weintraub
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-21 16:16:00ID requested
12022-03-28 22:30:50announced
Publication List
no publication
Keyword List
submitter keyword: Cell death, Endoplasmic reticulum stress, LIPA, Small molecule, Triple neggative breast cancer
Contact List
Ratna K Vadlamudi, Ph.D.
contact affiliationUT Health San Antonio
contact emailvadlamudi@uthscsa.edu
lab head
Susan T. Weintraub
contact affiliationUT Health Science Center San Antonio
contact emailweintraub@uthscsa.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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