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PXD035100

PXD035100 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression
DescriptionAnaplastic lymphoma kinase (ALK) fusion variants in non-small-cell-lung cancer (NSCLC) consist of numerous dimerising fusion partners, with the most common being EML4. Clinical data suggests that the degree of treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs among the variant present in the patient tumor. Therefore, a better understanding the oncogenic signaling networks driven by different ALK-fusion variants is important. Here, we developed highly controlled doxycycline-inducible cell models bearing four different ALK fusion proteins, namely EML4-ALK-V1, EML4-ALK-V3, KIF5B-ALK, and TFG-ALK, in the context of non-tumorigenic NL20 human bronchial epithelial cells. These were complimented by patient-derived NSCLC cell lines harboring either EML4-ALK-V1 or EML4-ALK-V3 fusions. RNAseq and phosphoproteomics analysis were employed to identify dysregulated genes and hyper/hypo-phosphorylated proteins associated with ALK fusion expression. Among ALK fusion induced responses, we noted a robust inflammatory signature that included up-regulation of the Serpin B4 serine protease inhibitor in both NL20-inducible cell models and ALK-positive NSCLC patient-derived cell lines. We show that STAT3 is a major transcriptional regulator of SERPINB4 downstream of ALK fusions, along with NF-B and AP1. The upregulation of SERPINB4 promotes survival of ALK fusion expressing cells and inhibits natural killer (NK) cell-mediated cytotoxicity. In conclusion, our study reveals a novel ALK downstream survival axis that regulates Serpin B4 expression and identifies a molecular target that has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:57:37.328.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJonatan Gabre
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-06 02:36:04ID requested
12023-02-16 01:30:36announced
22023-11-14 08:57:37announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, NSCLCL, Orbitrap Fusion Lumos
Contact List
Bengt Hallberg
contact affiliationDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Sweden.
contact emailbengt.hallberg@gu.se
lab head
Jonatan Gabre
contact affiliationUniversity of Gothenburg, Gothenburg, Sweden University of Ghent, Ghent, Belgium
contact emailjonatan.gabre@gu.se
dataset submitter
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