Changes in secreted proteins of oral squamous cell carcinoma (OSCC) cells under hyperglycemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Tomonori Sasahira
PROVIDER: PXD075712 | JPOST Repository | Mon May 11 00:00:00 BST 2026
REPOSITORIES: jPOST
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Project description: Not available
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Project description:<h4><strong>OBJECTIVE:</strong> Emerging evidence suggests that glucose depletion (GD)-induced cell death depends on system Xc-, a glutamate/cystine antiporter extensively studied in ferroptosis. However, the underlying mechanism remains debated. Our study confirmed the correlation between system Xc- and GD-induced cell death and provided a strategic treatment for oral squamous cell carcinoma (OSCC).</h4><p><strong>METHODS:</strong> qPCR and Western blotting were performed to detect changes in xCT and CD98 expression after glucose withdrawal. Then, the cell viability of OSCCs under the indicated conditions was measured. To identify the GD-responsible transcriptional factors of SLC7A11, we performed a luciferase reporter assay and a ChIP assay. Further, metabolomics was conducted to identify changes in metabolites. Finally, mitochondrial function and ATP production were evaluated using the seahorse assay, and NADP+/NADPH dynamics were measured using a NADP+/NADPH kit.</p><p><strong>RESULTS:</strong> In OSCCs, system Xc- promoted GD-induced cell death by increasing glutamate consumption, which promoted NADPH exhaustion and TCA blockade. Moreover, GD-induced xCT upregulation was governed by the p-eIF2α/ATF4 axis.</p><h4><strong>CONCLUSIONS:</strong> System Xc- overexpression compromised the metabolic flexibility of OSCC under GD conditions, and thus, glucose starvation therapy is effective for killing OSCC cells.</h4>
2024-01-16 | MTBLS5358 | MetaboLights
Project description:Oral squamous cell carcinoma (OSCC) is a main reason of oral cancer mortality and morbidity. Cancer of oral cavity in central south Asia, ranks among third most common kinds of cancer. The discovery of candidate markers to differentiate normal from malignant cells in clinical diagnosis of OSCC would be of critical importance because this malignancy has poor prognosis. To improve the clinical outcome in OSCC patients, the present study was aimed at identifying robust candidate biomarkers for early OSCC diagnosis and to enhance understanding of the mechanisms of disease progression and pathogenesis. Of particular interest are proteins that can be found in tissue lysates of OSCC tumor vs normal adjacent mucosa samples and secreted in cell line Secretomes of HNSCC for non-invasive detection. We analysed 17 paired human malignant OSCC tissues and normal adjacent tissue in addition to secretomes of 9 HNSCC cell lines. The proteome dataset of OSCC and normal tissues consisted of 5,123 protein groups, including 299 proteins with strong differential expression (p-value <0.01, fold change barrier to ?+2 and <-2, 205 upregulated and 94 down regulated) and 134 common proteins were also found out of total dataset of 4473 identified proteins of HNSCC cell line secretomes. Functional data analysis revealed that these differential proteins were significantly associated with multiple biological processes. Myogenesis, Fatty Acid Metabolism and KRAS Signaling DN were associated with the proteins downregulated in cancer tissues, while Protein Secretion, Unfolded Protein Response, Spliceosomal complex assembly, Protein localization to endosome and Interferon Gamma Response were enriched in the set of upregulated proteins and these regulated proteins may be classically or non-classically secreted. Furthermore, we found differential enrichment of Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP transcription factors potentially regulating these major pathways.
2025-10-07 | MSV000099414 | MassIVE
Project description:Oral squamous cell carcinoma (OSCC) is a main reason of oral cancer mortality and morbidity. Cancer of oral cavity in central south Asia, ranks among third most common kinds of cancer. The discovery of candidate markers to differentiate normal from malignant cells in clinical diagnosis of OSCC would be of critical importance because this malignancy has poor prognosis. To improve the clinical outcome in OSCC patients, the present study was aimed at identifying robust candidate biomarkers for early OSCC diagnosis and to enhance understanding of the mechanisms of disease progression and pathogenesis. Of particular interest are proteins that can be found in tissue lysates of OSCC tumor vs normal adjacent mucosa samples and secreted in cell line Secretomes of HNSCC for non-invasive detection. We analysed 17 paired human malignant OSCC tissues and normal adjacent tissue in addition to secretomes of 9 HNSCC cell lines. The proteome dataset of OSCC and normal tissues consisted of 5,123 protein groups, including 299 proteins with strong differential expression (p-value <0.01, fold change barrier to ˃+2 and <-2, 205 upregulated and 94 down regulated) and 134 common proteins were also found out of total dataset of 4473 identified proteins of HNSCC cell line secretomes. Functional data analysis revealed that these differential proteins were significantly associated with multiple biological processes. Myogenesis, Fatty Acid Metabolism and KRAS Signaling DN were associated with the proteins downregulated in cancer tissues, while Protein Secretion, Unfolded Protein Response, Spliceosomal complex assembly, Protein localization to endosome and Interferon Gamma Response were enriched in the set of upregulated proteins and these regulated proteins may be classically or non-classically secreted. Furthermore, we found differential enrichment of Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP transcription factors potentially regulating these major pathways.
2022-04-04 | PXD025701 | Pride
Project description:Lysate (1.5% SDS / 100 mm Tris-Cl) was added to samples on ice, mixed well and centrifuged to obtain supernatant. The protein concentration was determined by Bradford assay, and the protein bands were visualized by SDS-PAGE. Enzymatic digestion with trypsin was followed by Sep-Pak C18 desalting. Equal amounts of samples were taken for TMT labeling, which was performed according to the manufacturer's instructions. After equal mixing of the labeled samples, the pooled samples were fractionated by high pH reverse chromatography and checked on the machine. Mass spectrometry data were acquired using a liquid-mass coupled system with an Orbitrap Exploris 480 mass spectrometer in tandem with an EASY-nLC 1200 liquid phase. Mass spectrometric data were searched by MaxQuant (v1.6.6) software and the adopted database searching algorithm was Andromeda. The database used for the search was Swissprot Human (20210312) proteome reference databases.
2023-07-20 | PXD033080 | Pride
Project description:Analysis of DNA from 94 oral lesions by whole genome tiling-path array comparative genomic hybridization. Keywords: array comparative genomic hybridization
2008-12-31 | GSE9193 | GEO
Project description:Analysis of DNA from 94 oral lesions by whole genome tiling-path array comparative genomic hybridization. Keywords: array comparative genomic hybridization Whole genome tiling-path array CGH profiles of 94 formalin-fixed paraffin-embedded oral specimens.
2008-12-30 | E-GEOD-9193 | biostudies-arrayexpress
Project description:Canine Oral Squamous Cell Carcinoma (COSCC) is the second most common oral tumor in dogs, and the most relevant for comparative human trials as a spontaneous large animal model of disease. Thus, complete knowledge of the genomic landscape is essential for identifying therapeutic vulnerabilities and early biomarkers of disease across species. Historical genomic work has focused primarily on bulk sequencing, with only one publication using a laser capture dissection technique. The present study describes the complete molecular landscape of COSCC with spatial distinction between the surface tumor, deep invasive front, tumor microenvironment, and peritumoral dysplasia compared to matched normal samples. Each region demonstrated distinct molecular signatures. Genes related to epithelial growth factor (EGFR) and epithelial mesenchymal transformation (EMT) were upregulated in peri-tumoral dysplasia and surface cancer. Additionally, KRAS, SSP1 and KRT14 were upregulated in cancer, therefore combining these read outs may be useful in differentiating high grade dysplasia from malignant tissue at a molecular level. The primary tumor infiltrating leukocyte present in the tumor stroma were M2 macrophages. IL-10 expression was also significantly higher in the stroma, suggesting that tumor associated macrophages were directly related to establishing an immunosuppressive environment via cytokine secretion. The other predominant leukocytes were T-cells, with CD4+ T-cells being most common. CD4+ T cells expressed transcripts for both stimulatory (adaptive immunity with B cells and ICOS) and inhibitory molecules (CTLA4). However, the observed increase in CTLA4 suggests that this inhibitory signal may be preventing a robust anti-tumor immune response representing a therapeutic target for COSCC.
2025-06-26 | GSE292226 | GEO
Project description: Not available
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Project description:An investigation of canine oral squamous cell carcinomas
2024-06-30 | PRJEB77007 | EVA