PXD043220

PXD043220 is an original dataset announced via ProteomeXchange.

Title	Proteomic and phosphoproteomic reprogramming in epithelial ovarian cancer metastasis
Description	Epithelial ovarian cancer (EOC) is a high-risk cancer presenting with heterogeneous tumors. The high incidence of EOC metastasis from primary tumors to nearby tissues and organs is a major driver of EOC lethality. We used cellular models of spheroid formation and re-adherence to investigate cellular signaling dynamics in each step toward EOC metastasis. In our system, adherent cells model primary tumors, spheroids formation represents the initiation of metastatic spread, while re-adherent spheroid cells represent secondary tumors. Proteomic and phosphoproteomic analyses show that spheroid cells are hypoxic and show markers for cell cycle arrest. Aurora kinase B (AURKB) abundance and downstream substrate phosphorylation are significantly reduced in spheroids and re-adherent cells, explaining their cell cycle arrest phenotype. The proteome of re-adherent cells is most similar to spheroids, yet greater changes in the phosphoproteome show that spheroid cells stimulate Rho-associated kinase 1 (ROCK1) mediated signaling, which controls cytoskeletal organization. In spheroids, we found significant phosphorylation of ROCK1 substrates that were reduced in both adherent and re-adherent cells. Application of the ROCK1-specific inhibitor Y-27632 to spheroids increased the rate of re-adherence and spheroid density. The data suggest ROCK1 inhibition increases EOC metastatic potential. We identified novel pathways controlled by AURKB and ROCK1 as major drivers of metastatic behavior in EOC cells. Our data show that phosphoproteomic reprogramming precedes proteomic changes that characterize spheroid re-adherence in EOC metastasis.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_11:03:15.225.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Owen Hovey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-22 18:25:36	ID requested
⏵ 1	2024-01-26 11:03:16	announced

Frederick MI, Hovey OFJ, Kakadia JH, Shepherd TG, Li SSC, Heinemann IU, Proteomic and Phosphoproteomic Reprogramming in Epithelial Ovarian Cancer Metastasis. Mol Cell Proteomics, 22(11):100660(2023) [pubmed]

10.1016/j.mcpro.2023.100660;

submitter keyword: Aurora Kinase,Epithelial ovarian cancer, phosphoproteomics, Rock1, metastasis

Ilka Heinemann
contact affiliation	Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 5C1, Canada
contact email	iheinema@uwo.ca
lab head
Owen Hovey
contact affiliation	University of Western Ontario
contact email	ohovey@uwo.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043220
     1. Label: PRIDE project
     2. Name: Proteomic and phosphoproteomic reprogramming in epithelial ovarian cancer metastasis