PXD020590

PXD020590 is an original dataset announced via ProteomeXchange.

Title	LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma
Description	Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for proliferation and maintaining cell identity in MCC. There is growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.
HostingRepository	PRIDE
AnnounceDate	2020-11-03
AnnouncementXML	Submission_2020-11-03_06:47:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Imre
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylated residue; Hydroxytrimethyl; phosphorylated residue; deaminated residue; monohydroxylated residue; acetylated residue; dimethylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-27 02:38:06	ID requested
⏵ 1	2020-11-03 06:48:00	announced

Leiendecker L, Jung PS, Krecioch I, Neumann T, Schleiffer A, Mechtler K, Wiesner T, Obenauf AC, LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma. EMBO Mol Med, 12(11):e12525(2020) [pubmed]

submitter keyword: Epigenetics, MCC, LSD1, KDM1A, HMG20B

Anna Christina Obenauf
contact affiliation	Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria.
contact email	anna.obenauf@imp.ac.at
lab head
Richard Imre
contact affiliation	IMBA - Institute of Molecular Biotechnology
contact email	imre@imp.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020590
     1. Label: PRIDE project
     2. Name: LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma