MassIVE MSV000087385

Complete Public PXD025880

Protease activity profiling of ovarian clear cell carcinoma

Description

Ovarian clear cell carcinoma (OCCC) is an understudied poor prognosis subtype of ovarian cancer lacking in effective molecularly targeted therapies; efforts to define drivers of OCCC malignancy may lead to new therapeutic targets and approaches. Among potential targets are secreted proteases, enzymes which in many cancers serve as key drivers of malignant progression. To identify proteases responsible for the proteolytic landscape of the tumor microenvironment requires methods that directly report on enzyme activity, as transcript or protein abundance alone are poor indicators of protease activity. Here we developed an activity-based probe featuring an arginine diphenylphosphonate warhead to detect active serine proteases of trypsin-like specificity. A biotin handle was incorporated to facilitate affinity purification of labeled proteases. Using this probe, we employed activity-based protein profiling to identify active trypsin-like serine proteases within the complex proteome secreted by OCCC cell lines. We identified multiple active serine proteases in OCCC cell lines, including two proteases in common, tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Further interrogation of these proteases showed that both were involved in cancer cell invasion and proliferation of OCCC cells. The detection of tPA and uPA as catalytically active proteases and significant drivers of the malignant phenotype may point to these enzymes as targets for new therapeutic strategies in OCCC. Our activity-based probe and profiling methodology also offer a valuable tool for detection of active trypsin-like serine proteases in models of other cancers and other diseases. [doi:10.25345/C5C53S] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: serine protease, ovarian cancer, proteomics, proteolytic enzyme, peptidase, protein chemical modification, enzyme inhibitor, tumor microenvironment, activity-based probe, activity-based protein profiling (ABPP)

Contact

Principal Investigators:
(in alphabetical order)
Evette Radisky, Mayo Clinic, United States
Submitting User: MGFProteomicsCore

Publications

Mehner C, Hockla A, Coban M, Madden B, Estrada R, Radisky DC, Radisky ES.
Activity-based protein profiling reveals active serine proteases that drive malignancy of human ovarian clear cell carcinoma.
J Biol Chem. 2022 Aug;298(8):102146. Epub 2022 Jun 16.

Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files Browse Results
 
FTP Download Link (click to copy):

- Dataset Reanalyses


+ Dataset History


Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.