PXD034177

PXD034177 is an original dataset announced via ProteomeXchange.

Title	NADPH Oxidase 1 in Chronic Pancreatitis-Activated Pancreatic Stellate Cells Facilitates the Progression of Pancreatic Cancer
Description	Aims: Patients suffering from chronic pancreatitis (CP) have a higher risk of pancreatic ductal adenocarcinoma (PDAC). NADPH oxidase 1 (Nox1) in activated pancreatic stellate cells from a CP mouse model (CP-activated PaSCs) forms fibrotic tissue and up-regulates matrix metalloproteinase (MMP) 9. Yet, the role and mechanism of Nox1 in CP-activated PaSCs in the progression of PDAC is unknown. 1) We tested the ability of Nox1 in CP-activated PaSCs to facilitate the growth and invasion of pancreatic cancer cells. 2) We identified proteins in the secretome of CP-activated PaSCs whose production was Nox1-dependent. Results: In vitro, Nox1 in CP-activated PaSCs facilitated the migration/invasion of MIA PaCa-2 and HPAC cells. Nox1 evoked a both pro-invasive and cancer-promoting phenotype in PaSCs via a paracrine activation of both p38 MAPK and STAT3 pathways in neoplastic cells. In vivo, Nox1 in CP-activated PaSCs facilitated tumor growth, metastasis formation, and stromal expansion. Using mass spectrometry, we identified proteins protecting from cellular stresses in the secretome of CP-activated PaSCs whose production was Nox1-dependent. Innovation: Inhibiting the stromal Nox1 signaling at early stages can reduce the reorganization of histological barriers, and the protection of neoplastic cells from cellular stresses, ameliorating the progression of PDAC. Conclusions: Nox1 in CP-activated PaSCs induced both Twist1 and MMP-9 expression, causing changes in the extracellular matrix composition. In addition, Nox1 oxidized peroxiredoxins 1 and 4 through thioredoxin reductase 1, causing p38 MAPK and STAT3 phosphorylation in neoplastic cells when they were secreted from CP-activated PaSCs. Both mechanisms facilitated the progression of PDAC.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:12:31.549.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MARIA SABBATINI
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-29 13:43:33	ID requested
1	2023-03-10 13:16:17	announced
⏵ 2	2023-11-14 08:12:33	announced	2023-11-14: Updated project metadata.

Chakraborty A, Halder B, Mondal S, Barrett A, Zhi W, Csanyi G, Sabbatini ME, NADPH oxidase 1 in chronic pancreatitis-activated pancreatic stellate cells facilitates the progression of pancreatic cancer. Am J Cancer Res, 13(1):118-142(2023) [pubmed]

submitter keyword: NADPH oxidase 1

MMP-9

peroxiredoxin

Twist1

p38 MAPK

pancreatic stellate cells

MARIA EUGENIA SABBATINI
contact affiliation	Assistant Professor of Biological Sciences Augusta University C2014 Science Hall 2500 Walton Way, Augusta-GA
contact email	msabbatini@augusta.edu
lab head
MARIA SABBATINI
contact affiliation	augusta university
contact email	msabbatini@augusta.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034177
     1. Label: PRIDE project
     2. Name: NADPH Oxidase 1 in Chronic Pancreatitis-Activated Pancreatic Stellate Cells Facilitates the Progression of Pancreatic Cancer