PXD016244

PXD016244 is an original dataset announced via ProteomeXchange.

Title	Inhibition of Collagen XI alpha 1–induced Fatty Acid Oxidation Triggers Apoptotic Cell Death in Cisplatin-Resistant Ovarian Cancer
Description	Collagen type XI alpha 1 (COL11A1) is a novel biomarker associated with cisplatin resistance in ovarian cancer. However, the mechanisms underlying how COL11A1 confers cisplatin resistance in ovarian cancer are poorly understood. We identified that fatty acid β-oxidation (FAO) is upregulated by COL11A1 in ovarian cancer cells and that COL11A1-driven cisplatin resistance can be abrogated by inhibition of FAO. Furthermore, our results demonstrate that COL11A1 also enhances the expression of proteins involved in fatty acid synthesis. Interestingly, COL11A1-induced upregulation of fatty acid synthesis and FAO is modulated by the same signaling molecules. We identified that binding of COL11A1 to its receptors, α1β1 integrin and discoidin domain receptor 2 (DDR2), activates Src-Akt-AMPK signaling to increase the expression of both fatty acid synthesis and oxidation enzymes, although DDR2 seems to be the predominant receptor. Inhibition of fatty acid synthesis downregulates FAO despite the presence of COL11A1, suggesting that fatty acid synthesis might be a driver of FAO in ovarian cancer cells. Taken together, our results suggest that COL11A1 upregulates fatty acid metabolism in ovarian cancer cells in a DDR2-Src-Akt-AMPK dependent manner. Therefore, we propose that blocking FAO might serve as a promising therapeutic target to treat ovarian cancer, particularly cisplatin-resistant recurrent ovarian cancers which typically express high levels of COL11A1.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:02:44.525.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wei Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-12 02:46:08	ID requested
1	2020-04-27 22:06:55	announced
⏵ 2	2024-10-22 05:02:46	announced	2024-10-22: Updated project metadata.

Nallanthighal S, Rada M, Heiserman JP, Cha J, Sage J, Zhou B, Yang W, Hu Y, Korgaonkar C, Hanos CT, Ashkavand Z, Norman K, Orsulic S, Cheon DJ, Inhibition of collagen XI alpha 1-induced fatty acid oxidation triggers apoptotic cell death in cisplatin-resistant ovarian cancer. Cell Death Dis, 11(4):258(2020) [pubmed]

10.1038/s41419-020-2442-z;

submitter keyword: Proteomics

TMT

Collagen

Fatty acid oxidation

Ovarian cancer

Wei Yang
contact affiliation	Cedars-Sinai Medical Center
contact email	wei.yang@cshs.org
lab head
Wei Yang
contact affiliation	Stony Brook University
contact email	wei.yang@cshs.org
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/2020/04/PXD016244

PRIDE project URI

• PRIDE
  1. PXD016244
     1. Label: PRIDE project
     2. Name: Inhibition of Collagen XI alpha 1–induced Fatty Acid Oxidation Triggers Apoptotic Cell Death in Cisplatin-Resistant Ovarian Cancer