PXD010224

PXD010224 is an original dataset announced via ProteomeXchange.

Title	Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells
Description	Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely cures fatal acute promyelocytic leukemia, but the mechanisms underlying their action and synergy remain elusive. ATRA inhibits APL, breast and liver cancers by targeting isomerase Pin1, a master regulator of oncogenic signaling. Here we show that ATO targets Pin1 and cooperates with ATRA to exert potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its oncogenic function by noncovalent binding to Pin1’s active site. ATRA increases cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways and inhibit the growth of triple-negative breast cancer cells and tumor-initiating cells in cell and animal models including patient-derived orthotopic xenografts, similar to Pin1 CRISPR knockout, which is substantiated by comprehensive protein and microRNA analyses. Thus, synergistic Pin1 inhibition by ATO and ATRA offers an attractive approach to combating breast and other cancers.
HostingRepository	PRIDE
AnnounceDate	2018-10-16
AnnouncementXML	Submission_2018-10-16_08:59:22.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chenxi Qiu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-26 02:28:53	ID requested
⏵ 1	2018-10-16 08:59:23	announced

Kozono S, Lin YM, Seo HS, Pinch B, Lian X, Qiu C, Herbert MK, Chen CH, Tan L, Gao ZJ, Massefski W, Doctor ZM, Jackson BP, Chen Y, Dhe-Paganon S, Lu KP, Zhou XZ, Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun, 9(1):3069(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Pin1, ATO, ATRA, Synergy

Kun Ping Lu
contact affiliation	Beth Israel Deaconess Medical Center, Harvard Medical School, Broad Institute
contact email	klu@bidmc.harvard.edu
lab head
Chenxi Qiu
contact affiliation	Beth Israel Deaconess Medical Center
contact email	cqiu@bidmc.harvard.edu
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/2018/10/PXD010224

PRIDE project URI

• PRIDE
  1. PXD010224
     1. Label: PRIDE project
     2. Name: Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells