PXD049122 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | KANK1 inhibits the tumor suppressor Scribble by competing for NOS1AP binding |
Description | KANK1 belongs to the KANK family of scaffolding proteins that is expressed in epithelial cells and connects focal adhesions with the adjacent cortical microtubule stabilizing complex. Although KANK1 overexpression studies was shown to suppress the growth of different cancer cell lines in vitro, The Cancer Genome Atlas (TCGA) database indicates that high rather than low KANK1 levels are associated with poor prognosis in a wide spectrum of human malignancies. In the present study, we addressed this discrepancy and characterized how KANK1 regulates tumor development in the Polyoma Middle T (PyMT)-driven murine breast cancer model and upon orthotopic implantation of human breast cancer cells in immune-deficient mice. Our results revealed that KANK1 promotes cell proliferation and cell survival of PyMT-transformed tumor cells in vivo. Mechanistically, KANK1 localizes to the basal side of basement membrane (BM)-attached transformed luminal epithelial cells. However, when these cells detach from the BM and disassemble integrin adhesions, KANK1 translocates to cell-cell junctions where it competes with the polarity and tumor suppressor protein SCRIB for NOS1AP binding and thereby curbs the ability of SCRIB to activate the Hippo pathway. The consequences are stabilization and nuclear accumulation of TAZ, growth and survival of tumor cells and elevated breast cancer development. Importantly, the oncogenic pathway induced by KANK1 at cell-cell junctions also operates in human breast cancer. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:59:30.300.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Barbara Steigenberger |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF; timsTOF Pro |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-02-02 09:07:58 | ID requested | |
1 | 2024-09-24 04:02:32 | announced | |
⏵ 2 | 2024-10-22 06:59:30 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: cell-cell contacts, breast cancer,KANK1, TAZ and Hippo pathway |
Contact List
Shiny Shengzhen Guo1 |
contact affiliation | Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany |
contact email | shguo@biochem.mpg.de |
lab head | |
Barbara Steigenberger |
contact affiliation | MPI of Biochemistry |
contact email | steigenberger@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD049122
- Label: PRIDE project
- Name: KANK1 inhibits the tumor suppressor Scribble by competing for NOS1AP binding