PXD049122

PXD049122 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: cell-cell contacts, breast cancer,KANK1, TAZ and Hippo pathway

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

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/2024/09/PXD049122

PRIDE project URI

• PRIDE
  1. PXD049122
     1. Label: PRIDE project
     2. Name: KANK1 inhibits the tumor suppressor Scribble by competing for NOS1AP binding