PXD035770

PXD035770 is an original dataset announced via ProteomeXchange.

Title	Generation of fibronectin fragments by pancreatic trypsin: a physiological mechanism hampering PDAC progression.
Description	In this study we demonstrate that spheroids isolated from normal pancreas and co-trasplanted with PDAC orthotopically in mouse pancreas , inhibited tumor growth. Fibronectin proteolytic fragments generated by trypsin and released by pancreatic spheroids, were responsible for of the observed effect. Specifically, in vitro analysis revealed that FAK and FGFR1 signalling were turned off in tumor cells inducing tumor cell detachment, indicating a cooperative activity between the two signalling pathways. This mutual relationship was confirmed by the addition of FGF2 that reversed both FGFR1 and FAK defosphorilation and promoted PDAC cell adhesion and proliferation. Mass spectrometry proteomic analysis and the use of mAb allowed the identification of the FN fragments belonging to the Type III domain responsible of PDAC inhibition. Finally, the effect of FAK and FGFR signalling inhibitors was tested in combination both in vivo and in vitro to emulate the effect of normal pancreatic spheroids on PDAC growth.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:08:51.559.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Brunelli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-02 10:50:30	ID requested
1	2023-10-24 11:19:48	announced
2	2023-11-14 09:07:31	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:08:52	announced	2024-10-22: Updated project metadata.

Resovi A, Persichitti P, Brunelli L, Minoli L, Borsotti P, Garattini G, Tironi M, Dugnani E, Redegalli M, De Simone G, Pastorelli R, Bani MR, Piemonti L, Mosher DF, Giavazzi R, Taraboletti G, Belotti D, Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth. J Exp Clin Cancer Res, 42(1):201(2023) [pubmed]

10.1186/s13046-023-02778-y;

submitter keyword: PDAC, Trypsin, Fibronectin, FGFR, FAK

Roberta Pastorelli
contact affiliation	Istituto ricerche farmacologiche mario negri
contact email	roberta.pastorelli@marionegri.it
lab head
Laura Brunelli
contact affiliation	IRCCS Istituto Ricerche Farmacologiche Mario Negri
contact email	laura.brunelli@marionegri.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035770
     1. Label: PRIDE project
     2. Name: Generation of fibronectin fragments by pancreatic trypsin: a physiological mechanism hampering PDAC progression.