PXD012980-1

PXD012980 is an original dataset announced via ProteomeXchange.

Title	IL6/STAT3 co-opts ER regulatory elements to drive metastasis in breast cancer
Description	Interleukin 6 (IL6) signaling has been associated with an aggressive and metastatic phenotype in multiple solid tumors including breast cancer, but its mechanism of action in mediating tumor progression and treatment response is not clear. By exploiting a clinically relevant intraductal xenograft model of estrogen receptor positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. By integrating pre-clinical models and clinical specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancer-elements shared with ER and its pioneer factor FOXA1. Although IL6 activated STAT3 and ER/FOXA1 share cis-regulatory regions, STAT3 drives transcription independent of ER and FOXA1 function, and the IL6/STAT3 gene program is not influenced by ER-targeted therapies, decoupling these two important pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but independent actionable pathways controlling breast cancer progression.
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_09:28:39.800.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Igor Chernukhin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-05 07:39:23	ID requested
⏵ 1	2021-09-08 09:28:40	announced
2	2024-10-22 05:25:58	announced	2024-10-22: Updated project metadata.

Siersb, æ, k R, Scabia V, Nagarajan S, Chernukhin I, Papachristou EK, Broome R, Johnston SJ, Joosten SEP, Green AR, Kumar S, Jones J, Omarjee S, Alvarez-Fernandez R, Glont S, Aitken SJ, Kishore K, Cheeseman D, Rakha EA, D'Santos C, Zwart W, Russell A, Brisken C, Carroll JS, Enhancers to Drive Breast Cancer Metastasis. Cancer Cell, 38(3):412-423.e9(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: IL6, STAT3, cancer, metastasis

Jason Carroll, PhD FMedSci
contact affiliation	Cancer Research UK, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE
contact email	Jason.Carroll@cruk.cam.ac.uk
lab head
Igor Chernukhin
contact affiliation	Cancer research UK Cambridge university
contact email	igor.chernukhin@cruk.cam.ac.uk
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/2021/09/PXD012980

PRIDE project URI

• PRIDE
  1. PXD012980
     1. Label: PRIDE project
     2. Name: IL6/STAT3 co-opts ER regulatory elements to drive metastasis in breast cancer