PXD054783-1

PXD054783 is an original dataset announced via ProteomeXchange.

Title	CXCL12 restricts tumor growth by suppressing the Ras, ERK1/2, c-Myc and the immune checkpoint PDL1 pathways
Description	Cytokines constitute a family of proteins that are secreted by a broad variety of cells and modulate the immune response. CXCL12, along with its receptor CXCR4, are essential players in numerous biological processes. Dysregulation of their function can underlie the mechanisms(s) of several pathologies, including malignancies. Here, we demonstrate a rather unexpected effect of the cytokine and its receptor: in both cells and animal models, CXCL12 restricts tumorigenicity of the glioblastoma cells U87-MG and U-118, and of the breast cancer cell PyMT. Overexpression of CXCL12 inhibits activation of the proto-oncogene Ras which results in downregulation of its proliferative signals, such as reduced phosphorylation of the extracellular signal-regulated kinase 1/2 (ERK1/2), inhibition of c-Myc expression, and subsequent inhibition of cell cycle. Furthermore, CXCL12 induces downregulation of the growth differentiation factor 15 (GDF15), insulin-like growth factor-binding protein 6 (IGFBP6), and matrix metalloproteinase-3 (MMP3), which are implicated in the metastatic process. Indeed, monitoring cell migration in vitro and generation of metastases in mice demonstrate that CXCL12 slows the migration of U87-MG and PyMT cells. Remarkably, overexpression of CXCL12 also downregulates the cell surface immune checkpoint protein programmed cell death-ligand 1 (PDL1), as is evidence by enhanced recruitment of cytotoxic CD8 T cells. Overall, CXCL12 inhibits tumor growth through several distinct mechanisms: inhibition of cell cycle and migration, as well as impairment of immune checkpoint, thereby stimulating a strong host’s immune response. The mechanism(s) that renders CXCL12 a tumor promoting agent in certain cells, and a tumor suppressor in others has remained elusive.
HostingRepository	PRIDE
AnnounceDate	2024-11-28
AnnouncementXML	Submission_2024-11-28_06:52:02.597.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-11 07:44:39	ID requested
⏵ 1	2024-11-28 06:52:02	announced

Dataset with its publication pending

submitter keyword: PDL1, tumor suppression, cxcl12

Aaron Ciechanover
contact affiliation	The Rappaport Faculty of Medicine and Research Institute,Technion-Israel Institute of Technology,ISRAEL
contact email	aaroncie@technion.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
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/2024/11/PXD054783

PRIDE project URI

• PRIDE
  1. PXD054783
     1. Label: PRIDE project
     2. Name: CXCL12 restricts tumor growth by suppressing the Ras, ERK1/2, c-Myc and the immune checkpoint PDL1 pathways