PXD003670

PXD003670 is an original dataset announced via ProteomeXchange.

Title	Carcinoma-associated fibroblasts stimulate cancer cell invasion by mechanically remodeling the basement membrane
Description	The first step in metastasis is dissemination of tumor cells into the surrounding tissue, or stroma. In carcinomas, cancers of epithelial origin, tumor cells must first breach the basement membrane (BM), a network that encapsulates the tumor. As tumor progresses, other cell types that reside in the stroma, such as carcinoma-associated fibroblasts (CAFs) accumulate around the tumor. Whether CAFs can help cancer cells to breach the BM remains an open question. Here we show that CAFs promote cancer cell invasion by physically remodeling the BM. Using a novel 3D in vitro model we observed that primary CAFs isolated from colon cancer patients stimulate cancer cell invasion through a native mesenteric BM. This stimulated invasion is the result of the physical presence of CAFs rather than an increased invasive potential of cancer cells. In the presence of CAFs, cancer cells can invade the BM in a matrix metalloproteinase-independent manner. Using live imaging, we found that CAFs actively pull and stretch the BM, leading to the formation of gaps through which cancer cells can migrate. Notably, CAF-mediated gap-widening is independent of proteolysis but relies on actomyosin contractility. We propose that CAFs exert mechanical forces that alter the organization and the physical properties of the BM, making it permissive for cancer cell invasion.
HostingRepository	PRIDE
AnnounceDate	2017-09-18
AnnouncementXML	Submission_2018-07-03_08:03:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillaume Arras
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-02-22 00:46:09	ID requested
1	2017-09-18 00:27:32	announced
2	2017-11-08 04:42:29	announced	Updated publication reference for PubMed record(s): 28931556.
⏵ 3	2018-07-03 08:03:54	announced	Updated publication reference for PubMed record(s): 28931556.

Glentis A, Oertle P, Mariani P, Chikina A, El Marjou F, Attieh Y, Zaccarini F, Lae M, Loew D, Dingli F, Sirven P, Schoumacher M, Gurchenkov BG, Plodinec M, Vignjevic DM, Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane. Nat Commun, 8(1):924(2017) [pubmed]

Attieh Y, Clark AG, Grass C, Richon S, Pocard M, Mariani P, Elkhatib N, Betz T, Gurchenkov B, Vignjevic DM, 3-dependent fibronectin assembly. J Cell Biol, 216(11):3509-3520(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: basement membrane, cell invasion, CAF, SILAC, secretome

Damarys Loew
contact affiliation	Laboratoire de Spectrométrie de Masse Protéomique (LSMP), Institut Curie, PSL Research University, France
contact email	damarys.loew@curie.fr
lab head
Guillaume Arras
contact affiliation	Institut Curie
contact email	guillaume.arras@curie.fr
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/2017/09/PXD003670

PRIDE project URI

• PRIDE
  1. PXD003670
     1. Label: PRIDE project
     2. Name: Carcinoma-associated fibroblasts stimulate cancer cell invasion by mechanically remodeling the basement membrane