PXD006327-1

PXD006327 is an original dataset announced via ProteomeXchange.

Title	B-catenin downregulates Dicer to promote ovarian cancer metastasis
Description	Ovarian cancer is a nearly uniform lethal disease and its highly aggressive metastatic phenotype portends a poor prognosis. Lack of a well-controlled, relevant experimental model has been a major obstacle to identifying key molecules causing metastasis. Here we describe the creation of a new isogenic model of spontaneous human ovarian cancer metastasis exhibiting opposite phenotypes - highly metastatic (HM) and non-metastatic (NM) - both in vitro and in vivo. HM was unique in its ability to metastasize consistently to the peritoneum, mimicking the major dissemination route of human ovarian cancer. In contrast, NM failed to form detectable metastases although it was equally tumorigenic. Using comparative label-free quantitative LC-MS/MS, we identified b-catenin which we demonstrated for the first time a direct role in the pathogenesis of ovarian cancer metastasis. Our studies also revealed a previously unrecognized role of b-catenin in the downregulation of multiple microRNAs (miRNAs) through attenuating miRNA biogenesis by targeting Dicer, a key component of the microRNA processing machinery. One such downregulated miRNAs was miR-29s involved in epithelial-to-mesenchymal transition and subsequent stem cell traits. Silencing b-catenin or overexpressing Dicer or miR-29 mimics in HM significantly reduced the ability of these cells to migrate. B-catenin knockdown cells also failed to metastasize in an orthotopic model of ovarian cancer. Meta-analysis revealed an increase in CTNNB1 and a decrease in DICER1 expression levels in the high-risk group. These results uncover b-catenin as a critical player in promoting ovarian cancer aggressiveness and a new mechanism linking between b-catenin and miRNA downregulation underlying this process.
HostingRepository	PRIDE
AnnounceDate	2017-07-03
AnnouncementXML	Submission_2017-07-03_01:22:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yi Man Eva Fung
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-04-19 01:12:18	ID requested
⏵ 1	2017-07-03 01:22:57	announced
2	2024-10-22 04:37:34	announced	2024-10-22: Updated project metadata.

To SKY, Mak ASC, Eva Fung YM, Che CM, Li SS, Deng W, Ru B, Zhang J, Wong AST, -catenin downregulates Dicer to promote ovarian cancer metastasis. Oncogene, 36(43):5927-5938(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: ovarian cancer, metastasis, -catenin, Dicer, microRNA

Chi-Ming Che
contact affiliation	Department of Chemistry, Chemical Biology Centre and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong
contact email	cmche@hku.hk
lab head
Yi Man Eva Fung
contact affiliation	The University of Hong Kong
contact email	eva.fungym@hku.hk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006327
     1. Label: PRIDE project
     2. Name: B-catenin downregulates Dicer to promote ovarian cancer metastasis