PXD008724-2

PXD008724 is an original dataset announced via ProteomeXchange.

Title	APIM-peptide targeting PCNA improves cisplatin therapy in a rat muscle-invasive bladder cancer model
Description	High mortality rate of muscle-invasive bladder cancer (MIBC) and complexity of disease demand new multi-targeting treatment strategies. Targeting proliferating cell nuclear antigen (PCNA) with a peptide containing the AlkB homologue 2 PCNA interacting motif (APIM), is shown to impair multiple vital cellular stress responses and induce hypersensitivity against several chemotherapeutics in different pre-clinical models. This study examine the anti-cancer efficacy of the novel APIM-peptide drug when combined with cisplatin-based therapies (cisplatin, cisplatin/gemcitabine (GC) and methotrexate/vinblastine/adriamycin/cisplatin (MVAC)) in a panel of bladder cancer (BC) cells and with intravenous cisplatin-therapy in a rat MIBC-model. Furthermore, we explore the molecular mechanisms underlying the observed effects on a genomic, proteomic and metabolomic level using microarray, multiplexed inhibitor bead (MIB)-assay, and targeted mass spectrometric metabolite profiling. The APIM-peptide significantly increased the efficacy of all cisplatin-based therapies in all BC cell lines tested, including a cisplatin resistant cell line and reduced the tumor load in cisplatin treated MIBC-bearing rats. Genome and proteome analysis of APIM-peptide/cisplatin treated BC cells revealed reduced expression of multiple proteins frequently overexpressed in MIBC. Of notice, the EGFR/ERBB2, PI3K/Akt and MAPK signaling pathways and anti-apoptosis were downregulated. We suggest that the anti-cancer effect of the APIM-peptide is through the downregulation of several known oncogenic signaling pathways including anti-apoptosis. Together our results indicate that the APIM-peptide represents a potential improved treatment approach for patients with MIBC.
HostingRepository	PRIDE
AnnounceDate	2018-09-10
AnnouncementXML	Submission_2018-09-13_02:33:21.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Animesh Sharma
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-19 06:00:59	ID requested
1	2018-09-10 04:17:40	announced
⏵ 2	2018-09-13 02:33:22	announced	Updated publication reference for PubMed record(s): 30197755.

S, ø, gaard CK, Blindheim A, R, ø, st LM, Petrovi, ć V, Nepal A, Bachke S, Liabakk NB, Gederaas OA, Viset T, Arum CJ, Bruheim P, Otterlei M, "Two hits - one stone"

increased efficacy of cisplatin-based therapies by targeting PCNA's role in both DNA repair and cellular signaling. Oncotarget, 9(65):32448-32465(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: rat, mib, assay, ay-27, lfq

Marit Otterlei
contact affiliation	Professor Institutt for klinisk og molekylær medisin Norges teknisk-naturvitenskapelige universitet Erling Skjalgssons g 1, Laboratoriesenteret * 231.05.036 Trondheim 7030 Norway
contact email	marit.otterlei@ntnu.no
lab head
Animesh Sharma
contact affiliation	Engineer at NTNU, Norway
contact email	sharma.animesh@gmail.com
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/2018/09/PXD008724

PRIDE project URI

• PRIDE
  1. PXD008724
     1. Label: PRIDE project
     2. Name: APIM-peptide targeting PCNA improves cisplatin therapy in a rat muscle-invasive bladder cancer model