PXD012694

PXD012694 is an original dataset announced via ProteomeXchange.

Title	RASSF1A controls Tissue Stiffness and Cancer Stem-like Cells in Lung Adenocarcinoma
Description	Lung cancer remains the leading cause of cancer-related death due to poor treatment responses and resistance arising from tumor heterogeneity. Here we show that adverse prognosis associated with epigenetic silencing of the tumour suppressor RASSF1A is due to increased deposition of extracellular matrix (ECM), tumour stiffness and metastatic dissemination in vitro and in vivo. We find that lung cancer cells with RASSF1A promoter methylation display constitutive nuclear YAP1 and expression of collagen prolylhydroxylase (P4HA2) which increases collagen deposition. Furthermore, we identify that elevated collagen creates a stiff-ECM which in turn triggers cancer stem-like programming and metastatic dissemination in vivo. Re-expression of RASSF1A or inhibition of P4HA2 activity reverse these effects and increase markers of lung differentiation (TTF-1, Mucin5B). Our study identifies RASSF1A as a clinical biomarker associated with mechanical properties of ECM which increases levels of cancer stemness and risk of metastatic progression in lung adenocarcinoma. Moreover, we highlight P4HA2 as a potential target for uncoupling ECM signals that support cancer stemness.
HostingRepository	PRIDE
AnnounceDate	2019-05-20
AnnouncementXML	Submission_2019-05-31_02:36:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-13 07:49:01	ID requested
1	2019-05-19 23:58:57	announced
⏵ 2	2019-05-31 02:36:28	announced	Updated publication reference for PubMed record(s): 31133556.

submitter keyword: cancer stem cells, Hippo pathway, stiffness, extracellular matrix.

Eric O'Neil
contact affiliation	Dept. of Oncology, University of Oxford, Oxford, OX3 7DQ, UK
contact email	eric.oneill@oncology.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	CRUK-MRC Oxford Institute for Radiation Oncology, Oxford University
contact email	iolanda.vendrell@oncology.ox.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/2019/05/PXD012694

PRIDE project URI

• PRIDE
  1. PXD012694
     1. Label: PRIDE project
     2. Name: RASSF1A controls Tissue Stiffness and Cancer Stem-like Cells in Lung Adenocarcinoma