PXD034155

PXD034155 is an original dataset announced via ProteomeXchange.

Title	LOSS OF DKC1 IN CUTANEOUS SQUAMOUS CELL CARCINOMA RESULTS IN A METABOLIC REWIRING AND THE ACQUISITION OF METASTATIC TRAITS LOSS OF DKC1 RESULTS IN THE ACQUISITION OF A LIPIDIC METABOLISM AND METASTATIC TRAITS IN CUTANEOUS SQUAMOUS CELL CARCINOMA OTROS TITULOS
Description	Metastaticsis disease remains, by far, the leading cause of all cancer-related deaths, despite being a process highly inefficient. The metastatic process is highly inefficient as the initial dissemination of cancer cells from many primary tumors involves intravasation to lymphatics nodes or blood vessels, a process poorly understood. To investigate generalthe molecular mechanisms involved in this step we analyzed the expression of the epigenetic regulators small non-coding RNAs (sncRNAs) in cutaneous squamous cell carcinoma (cSCC), a highly prevalent malignant tumor that mainly spreads to lymph nodes. Here we report the reduced expression of small nucleolar RNAs (snoRNAs) in primary cSCCs that metastasized when compared to non-metastasizing cSCCs, and the progressive loss of DKC1 (the protein that stabilizes the snoRNAs) along the metastasis of the carcinomas. DWe demonstrate that depletion of DKC1 in cSCC cells resulted in a switch totriggers lipid metabolism and the acquisition of metastatic traits. Treatment of DKC1-depleted cells with simvastatin, an inhibitor of the mevalonate pathway, blocked the expression of proteins involved in the epithelial to mesenchymal transition (EMT), suggesting that the rewiring of the lipid metabolism is required to acquire the invasion abilities. Furthermore, the expression of the enzyme HMGCS1 is associated with pathologic features of high metastatic risk in cSCC patients, underpinning the relevance of the mevalonate metabolism in the lymphatic dissemination step.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:48.844.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	guadalupe espadas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-27 06:20:46	ID requested
1	2023-01-31 02:20:22	announced
⏵ 2	2023-11-14 08:56:49	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Metabolism, epigenetics, Squamous Cell Carcinoma, snoRNA, DKC1, Metastasis,LC-MSMS

Eduard Sabidó
contact affiliation	Centre for Genomic Regulation (CRG)
contact email	eduard.sabido@crg.eu
lab head
guadalupe espadas
contact affiliation	crg
contact email	guadalupe.espadas@crg.eu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034155
     1. Label: PRIDE project
     2. Name: LOSS OF DKC1 IN CUTANEOUS SQUAMOUS CELL CARCINOMA RESULTS IN A METABOLIC REWIRING AND THE ACQUISITION OF METASTATIC TRAITS LOSS OF DKC1 RESULTS IN THE ACQUISITION OF A LIPIDIC METABOLISM AND METASTATIC TRAITS IN CUTANEOUS SQUAMOUS CELL CARCINOMA OTROS TITULOS