Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas
High-grade gliomas (HGG) are highly aggressive tumors, which are predominately fatal for adults and pediatric patients. Identifying cancer-selective therapeutic targets remains a critical unmet need. The overexpression of endoplasmic reticulum (ER) chaperones in various cancers is well documented. M...
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2025
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| _version_ | 1849927635154501632 |
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| author | Alexis Z Minchaca (22680460) |
| author2 | Jean Bertoldo (4920244) Philipp Graber (22680463) Dong-Hun Bae (22680466) Nisitha Jayatilleke (15031800) Chelsea Mayoh (9459377) Brett W. Stringer (7216580) Louise Ludlow (13519387) Maria Kavallaris (54201) Angelica M. Merlot (22680469) |
| author2_role | author author author author author author author author author |
| author_facet | Alexis Z Minchaca (22680460) Jean Bertoldo (4920244) Philipp Graber (22680463) Dong-Hun Bae (22680466) Nisitha Jayatilleke (15031800) Chelsea Mayoh (9459377) Brett W. Stringer (7216580) Louise Ludlow (13519387) Maria Kavallaris (54201) Angelica M. Merlot (22680469) |
| author_role | author |
| dc.creator.none.fl_str_mv | Alexis Z Minchaca (22680460) Jean Bertoldo (4920244) Philipp Graber (22680463) Dong-Hun Bae (22680466) Nisitha Jayatilleke (15031800) Chelsea Mayoh (9459377) Brett W. Stringer (7216580) Louise Ludlow (13519387) Maria Kavallaris (54201) Angelica M. Merlot (22680469) |
| dc.date.none.fl_str_mv | 2025-11-25T10:05:06Z |
| dc.identifier.none.fl_str_mv | 10.1021/acs.jproteome.5c00616.s009 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Surface_Proteomic_Analysis_Reveals_the_Presence_of_Noncanonical_Cell_Membrane_Endoplasmic_Reticulum_Chaperones_in_High-Grade_Gliomas/30704863 |
| dc.rights.none.fl_str_mv | CC BY-NC 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biochemistry Cell Biology Genetics Biotechnology Cancer Science Policy Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified tumor cells exhibit often escape detection highly aggressive tumors critical unmet need conventional bioinformatic pipelines surface expression levels atypical surface expression cancer selective targets surface protein levels grade gliomas high surface expression grade gliomas selective targeting identifying cancer well documented various cancers transcriptomics alone total protein surfaceome studies surfaceome analysis study examined study advances predominately fatal poor correlation pediatric patients neoplastic samples first time findings highlight endoplasmic reticulum devastating disease also highlight |
| dc.title.none.fl_str_mv | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | High-grade gliomas (HGG) are highly aggressive tumors, which are predominately fatal for adults and pediatric patients. Identifying cancer-selective therapeutic targets remains a critical unmet need. The overexpression of endoplasmic reticulum (ER) chaperones in various cancers is well documented. Moreover, tumor cells exhibit an atypical surface expression of ER chaperones, suggesting the potential for selective targeting. Our study examined the differences in the mRNA, total protein, and surface expression levels of seven key ER chaperones, compared with those in non-neoplastic samples. Notably, a poor correlation was found between mRNA, protein, and surface protein levels, underscoring the limitations of transcriptomics alone in target discovery. We also highlight the limitations of surfaceome studies which exclude noncanonical membrane proteins, such as ectopically expressed ER chaperones, which often escape detection by conventional bioinformatic pipelines. For the first time, this study advances our understanding of the surface expression of ER chaperones in both adult and pediatric HGG. Our findings highlight the importance of surfaceome analysis in the discovery of cancer selective targets against this devastating disease. |
| eu_rights_str_mv | openAccess |
| id | Manara_1afa36715c4a998bdcf97dc27cfa03b6 |
| identifier_str_mv | 10.1021/acs.jproteome.5c00616.s009 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30704863 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC 4.0 |
| spelling | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade GliomasAlexis Z Minchaca (22680460)Jean Bertoldo (4920244)Philipp Graber (22680463)Dong-Hun Bae (22680466)Nisitha Jayatilleke (15031800)Chelsea Mayoh (9459377)Brett W. Stringer (7216580)Louise Ludlow (13519387)Maria Kavallaris (54201)Angelica M. Merlot (22680469)BiochemistryCell BiologyGeneticsBiotechnologyCancerScience PolicyBiological Sciences not elsewhere classifiedChemical Sciences not elsewhere classifiedtumor cells exhibitoften escape detectionhighly aggressive tumorscritical unmet needconventional bioinformatic pipelinessurface expression levelsatypical surface expressioncancer selective targetssurface protein levelsgrade gliomas highsurface expressiongrade gliomasselective targetingidentifying cancerwell documentedvarious cancerstranscriptomics alonetotal proteinsurfaceome studiessurfaceome analysisstudy examinedstudy advancespredominately fatalpoor correlationpediatric patientsneoplastic samplesfirst timefindings highlightendoplasmic reticulumdevastating diseasealso highlightHigh-grade gliomas (HGG) are highly aggressive tumors, which are predominately fatal for adults and pediatric patients. Identifying cancer-selective therapeutic targets remains a critical unmet need. The overexpression of endoplasmic reticulum (ER) chaperones in various cancers is well documented. Moreover, tumor cells exhibit an atypical surface expression of ER chaperones, suggesting the potential for selective targeting. Our study examined the differences in the mRNA, total protein, and surface expression levels of seven key ER chaperones, compared with those in non-neoplastic samples. Notably, a poor correlation was found between mRNA, protein, and surface protein levels, underscoring the limitations of transcriptomics alone in target discovery. We also highlight the limitations of surfaceome studies which exclude noncanonical membrane proteins, such as ectopically expressed ER chaperones, which often escape detection by conventional bioinformatic pipelines. For the first time, this study advances our understanding of the surface expression of ER chaperones in both adult and pediatric HGG. Our findings highlight the importance of surfaceome analysis in the discovery of cancer selective targets against this devastating disease.2025-11-25T10:05:06ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.1021/acs.jproteome.5c00616.s009https://figshare.com/articles/dataset/Surface_Proteomic_Analysis_Reveals_the_Presence_of_Noncanonical_Cell_Membrane_Endoplasmic_Reticulum_Chaperones_in_High-Grade_Gliomas/30704863CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307048632025-11-25T10:05:06Z |
| spellingShingle | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas Alexis Z Minchaca (22680460) Biochemistry Cell Biology Genetics Biotechnology Cancer Science Policy Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified tumor cells exhibit often escape detection highly aggressive tumors critical unmet need conventional bioinformatic pipelines surface expression levels atypical surface expression cancer selective targets surface protein levels grade gliomas high surface expression grade gliomas selective targeting identifying cancer well documented various cancers transcriptomics alone total protein surfaceome studies surfaceome analysis study examined study advances predominately fatal poor correlation pediatric patients neoplastic samples first time findings highlight endoplasmic reticulum devastating disease also highlight |
| status_str | publishedVersion |
| title | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| title_full | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| title_fullStr | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| title_full_unstemmed | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| title_short | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| title_sort | Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas |
| topic | Biochemistry Cell Biology Genetics Biotechnology Cancer Science Policy Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified tumor cells exhibit often escape detection highly aggressive tumors critical unmet need conventional bioinformatic pipelines surface expression levels atypical surface expression cancer selective targets surface protein levels grade gliomas high surface expression grade gliomas selective targeting identifying cancer well documented various cancers transcriptomics alone total protein surfaceome studies surfaceome analysis study examined study advances predominately fatal poor correlation pediatric patients neoplastic samples first time findings highlight endoplasmic reticulum devastating disease also highlight |