DOI: 10.25345/c5vx06744
title: MassIVE MSV000090805 - Liver lineage confers sensitivity of cancer cells to sulfonation-dependent alkylators: Cell Lines
title: 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. (i) and (ii): Cell line samples from datasets (i) and (ii) were analyzed together in a set of 12 TMT sets (ShiBardeesy_CellLines_TMT1 to TMT12) using TMT11-barcoding. The samples were analyzed on an Orbitrap Lumos mass spectrometer using the SPS-MS3 method. Prior to analysis, samples were fractionated offline using high pH reversed chromatography (12 fractions per TMT set). Across all TMT sets, channel 131c was used as the bridge channel (pooled digests of all samples). Samples were labeled as follows (rep = replicate: (i) Cell lines samples with acquired resistance to YC-1 treatment: ShiBardeesy_CellLines_TMT1: RBE_rep_1 (126), RBE YC1 Resistant 6_rep_1 (129c). ShiBardeesy_CellLines_TMT2: RBE YC1 Resistant 3_rep_1 (129n), RBE YC1 Resistant 1_rep_1 (130n). ShiBardeesy_CellLines_TMT3: RBE YC1 Resistant 2_rep_1 (126), RBE YC1 Resistant 5_rep_1 (130c). ShiBardeesy_CellLines_TMT4: RBE YC1 Resistant 4_rep_1 (126). ShiBardeesy_CellLines_TMT5: RBE YC1 Resistant 1_rep_2 (127n), RBE YC1 Resistant 4_rep_2 (128c), RBE YC1 Resistant 3_rep_2 (130c). ShiBardeesy_CellLines_TMT6: RBE YC1 Resistant 2_rep_2 (126), RBE YC1 Resistant 6_rep_2 (127c). ShiBardeesy_CellLines_TMT7: RBE_rep_2 (128n), RBE YC1 Resistant 5_rep_2 (130n). (ii) Proteomes of untreated biliary cell lines (baseline): ShiBardeesy_CellLines_TMT1: RBE_rep_1 (126), GB2_rep_1 (127n), HuCCT1_rep_1 (127c), ECC3_rep_1 (128n), ICC10_rep_1 (128c), KMCH-1_rep_1 (129n), SNU-1196_rep_1 (130n). ShiBardeesy_CellLines_TMT2: ICC13-7_rep_1 (126), ICC8_rep_1 (127n), ICC9_rep_1 (127c), SNU-478_rep_1 (128n), CC-SW-1_rep_1 (128c), CC-LP-1_rep_1 (129c), SSP-25_rep_1 (130c), ICC10-8_rep_1 (131n) ShiBardeesy_CellLines_TMT3: SNU-1079_rep_1 (127n), ICC5_rep_1 (127c), ICC7_rep_1 (128c), COR-L105_rep_1 (129n), ICC17_rep_1 (129c), GBC1_rep_1 (131n). ShiBardeesy_CellLines_TMT4: ICC3_rep_1 (127n), ICC2_rep_1 (127c), ICC106_rep_1 (128n), ICC11_rep_1 (128c), HKGZ-CC_rep_1 (129n), SNU-869_rep_1 (129c), HuH28_rep_1 (130n), ICC12_rep_1 (130c), SNU-308_rep_1 (131n). ShiBardeesy_CellLines_TMT5: ICC2_rep_2 (126), ECC3_rep_2 (127c), GB2_rep_2 (128n), ICC11_rep_2 (129n), ICC7_rep_2 (129c), SNU-869_rep_2 (130n), SSP-25_rep_2 (131n). ShiBardeesy_CellLines_TMT6: CC-LP-1_rep_2 (127n), COR-L105_rep_2 (128n), HuCCT1_rep_2 (129n), ICC12_rep_2 (129c), ICC3_rep_2 (131n), ICC5_rep_2 (130n), SNU-478_rep_2 (130c). ShiBardeesy_CellLines_TMT7: ICC10_rep_2 (126), ICC10-6_rep_2 (127n), ICC10-8_rep_2 (127c), RBE_rep_2 (128n), ICC9_rep_2 (128c), ICC17_rep_2 (129n), ICC8_rep_2 (129c), CC-SW-1_rep_2 (130c), GBC1_rep_2 (131n). ShiBardeesy_CellLines_TMT8: ICC13-7_rep_2 (127c), HuH28_rep_2 (128n), HKGZ-CC_rep_2 (128c), SNU-1079_rep_2 (129n), KMCH-1_rep_2 (129c), SNU-1196_rep_2 (130n), SNU-308_rep_2 (131n). ShiBardeesy_CellLines_TMT9: SG231_rep_1 (126), KKU-100_rep_1 (127n), YSCCC_rep_1 (127c), ICC4_rep_1 (128n), TKKK_rep_1 (128c), ECC2_rep_1 (129n), KKU-M213/M214 (129c). ShiBardeesy_CellLines_TMT10: YSCCC_rep_2 (126), KKU-M213/M214_rep_2 (127n), SG231_rep_2 (127c), TKKK_rep_2 (129n), ECC2_rep_2 (129c), ICC4_rep_2 (130n), KKU-100_rep_2 (131n). ShiBardeesy_CellLines_TMT11: ICC13-7_rep_1 (129n). ShiBardeesy_CellLines_TMT12: ICC13-7_rep2 (131n)