MassIVE MSV000090808

Partial Public

Liver lineage confers sensitivity of cancer cells to sulfonation-dependent alkylators: PDX and Immobilized Drug Enrichment

Subscribe Comment Convert Spectra Add Reanalysis

Description

The small molecule YC-1 was identified as identified as a selectively active agent against subsets of the two major live cancer subtypes, intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Response to YC-1 is dependent on the expression of the sulfotransferase SULT1A1, which activates YC-1 through sulfonation. The contributions of mass spectrometry to the study were: (i) identifying SULT1A1 as the key player in YC-1 response through observing the protein in a cell line with acquired resistance to the small molecule treatment, (ii) corroborating the role of SULT1A1 in the YC-1 activity by correlating protein expression profiles and drug responses across 37 biliary cancer cell lines, (iii) showing that SULT1A1 expression was associated with IDH mutations, FGFR2 fusion, and BAP1 loss in vivo studying patient-derived xenograft (PDX) models, and (iv) identifying protein targets in a protein enrichment experiment with an immobilized drug. (iii) PDX samples were analyzed using TMT multiplexing on an Orbitrap Fusion mass spectrometer using the SPS-MS3 method. Prior to analysis, samples were fractionated offline using high pH reversed chromatography (12 fractions per TMT set). Three TMT sets were analyzed (ShiBardeesy_PDX_TMT1, ShiBardeesy_PDX_TMT2, and ShiBardeesy_PDX_TMT3), and samples were labeled as follows with channel (bridge channel, 130c): ShiBardeesy_PDX_TMT1: SS101 (126), MG12 (127c), SS106 (127n), MG62 (128c), MG26 (128n), LCCH13 (129c), LCCH3 (129n), Q12050 (130n). ShiBardeesy_PDX_TMT2: SS102 (126), SS110 (127n), MG34 (128c), MG17 (128n), LCCH4 (129c), MG68 (129n), HBT110 (130n). ShiBardeesy_PDX_TMT3: SS103 (126), MG10 (127n), MG59 (128c), MG25 (128n), LCCH10 (129c), MG73 (129n), HBT211 (130n). (iv) Samples from experiments using immobilized small molecules to determine direct interactors of YC-1 were performed using TMT10-barcoding and the SPS-MS3 method on an Orbitrap Lumos mass spectrometer. No off-line fraction was performed. Samples were grouped into two TMT sets (ShiBardeesy_ImmobilizedDrug_TMT1 and ShiBardeesy_ImmobilizedDrug_TMT2). Channel 131N was used as the bridge channel. Samples were labeled as follows: ShiBardeesy_ImmobilizedDrug_TMT1: immobilized_inactiveYC-1_rep_1 (126), immobilized_inactiveYC-1_rep_2 (128n), immobilized_inactiveYC-1_rep_3 (128c), immobilized_YC-1_rep_1 (129n), immobilized_YC-1_plus_soluble_YC-1_competitor_rep_1 (130c). ShiBardeesy_ImmobilizedDrug_TMT2: immobilized_YC-1_rep_2 (127n), immobilized_YC-1_plus_soluble_YC-1_competitor_rep_2 (128n), immobilized_YC-1_plus_soluble_YC-1_competitor_rep_3 (129c), immobilized_YC-1_rep_3 (130c). [doi:10.25345/C5GM81T27] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: liver cancer, small molecule YC-1, activity, target proteins, TMT multiplexed proteomics, SPS-MS3

Contact

Principal Investigators:
(in alphabetical order) 		Nabeel Bardeesy, Massachusetts General Hospital and Harvard Medical School, United States
Submitting User: whaas
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
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- 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.