PXD028495

PXD028495 is an original dataset announced via ProteomeXchange.

Title	Polo-like kinase 1 inhibitors differentiate triple-negative breast cancer towards a luminal cell fate
Description	Plasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, triple-negative is the subtype that lacks the expression of major differentiation markers (i.e. estrogen receptor  [ER]), ant its high cellular plasticity results in higher aggressiveness and poor prognosis compared to other subtypes. Whether plasticity poses a vulnerability to cancer cells remains elusive. Here, we show that cancer cell plasticity can be exploited to differentiate triple-negative breast cancer. Using a high-throughput reporter drug screen with 9,501 compounds, we identify three polo-like kinase 1 (PLK1) inhibitors as major inducers of ER protein expression and downstream activity in triple-negative breast cancer cells via the transcription factor BATF. PLK1 inhibition upregulates a cell differentiation program characterized by increased DNA damage, mitotic arrest and ultimately cell death. Notably, cells surviving PLK1 inhibition have decreased tumorigenic potential, and targeting PLK1 in already established tumours reduces tumour growth both in cell line and patient-derived xenograft models. In addition, genes upregulated upon PLK1 inhibition are correlated with expression in normal breast tissue and confer better overall survival in breast cancer patients. Our results indicate that differentiation therapy based on PLK1 inhibition might be an alternative strategy to treat triple-negative breast cancer.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:56.029.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028495
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Schmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-15 23:41:06	ID requested
1	2022-08-23 09:30:44	announced
⏵ 2	2023-11-14 08:52:56	announced	2023-11-14: Updated project metadata.

10.6019/PXD028495;

submitter keyword: Phosphoproteomics, LC-MS, PLK1,Breast Cancer

Alexander Schmidt
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028495
     1. Label: PRIDE project
     2. Name: Polo-like kinase 1 inhibitors differentiate triple-negative breast cancer towards a luminal cell fate