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PXD022596-1

PXD022596 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSOX4 AND SMARCA4 COOPERATIVELY REGULATE PI3K SIGNALING THROUGH TRANSCRIPTIONAL ACTIVATION OF TGFBR2 IN TRIPLE NEGATIVE BREAST CANCER
DescriptionDysregulation of PI3K/Akt signaling is a dominant feature in basal-like or triple-negative breast cancers (TNBC). However, the mechanisms regulating this pathway are largely unknown in this subset of aggressive tumors. Here we demonstrate that the transcription factor SOX4 is a key regulator of PI3K signaling in TNBC. Genomic and proteomic analyses coupled with mechanistic studies identified TGFBR2 as a direct transcriptional target of SOX4 and demonstrated that TGFBR2 is required to mediate SOX4-dependent PI3K signaling. We further report that SOX4 and the SWI/SNF ATPase SMARCA4, which are uniformly overexpressed in basal-like tumors, form a previously unreported complex that is required to maintain an open chromatin conformation at the TGFBR2 regulatory regions in order to mediate TGFBR2 expression and PI3K signaling. Collectively, our findings delineate the mechanism by which SOX4 and SMARCA4 cooperatively regulate PI3K/Akt signaling and suggest that this complex may play an essential role in TNBC genesis and/or progression. Kinase enrichment proteomic analysis was performed using HCC1143 breast cancer cells treated with a control siRNA pool or a pool targeting SOX4 in biological triplicate to evaluate the effects on the functional kinome.
HostingRepositoryPRIDE
AnnounceDate2021-03-03
AnnouncementXMLSubmission_2021-03-02_22:29:45.648.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSteven Angus
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-11-18 01:40:29ID requested
12021-03-02 22:29:46announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SOX4, TGFBR2, SMARCA4, SWI/SNF, PI3 kinase, transcription, chromatin, epigenetics, breast cancer
Contact List
Michael L. Gatza, PhD
contact affiliationDepartment of Radiation Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
contact emailmichael.gatza@cinj.rutgers.edu
lab head
Steven Angus
contact affiliationIndiana University School of Medicine
contact emailsangus@iu.edu
dataset submitter
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Dataset FTP location
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