Functional Proteomics of Breast Cancer Metabolism Identifies GLUL as Responder during Hypoxic Adaptation
| العنوان: | Functional Proteomics of Breast Cancer Metabolism Identifies GLUL as Responder during Hypoxic Adaptation |
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| المؤلفون: | Karin Müller-Decker, Jens Timmer, Christian Tönsing, Nese Erdem, Ulrike Korf, Stefan Wiemann, Devina Mitra, Stephan Bernhardt, Clemens Kreutz |
| المصدر: | Journal of Proteome Research. 18:1352-1362 |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Proteomics, 0301 basic medicine, Proteome, Lactate dehydrogenase A, Breast Neoplasms, medicine.disease_cause, Biochemistry, Mice, 03 medical and health sciences, Breast cancer, Glutamate-Ammonia Ligase, medicine, Animals, Humans, education, Glucose Transporter Type 1, education.field_of_study, L-Lactate Dehydrogenase, 030102 biochemistry & molecular biology, biology, Effector, Glucose transporter, General Chemistry, Metabolism, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Gene Expression Regulation, Neoplastic, Oxygen, 030104 developmental biology, MCF-7 Cells, Cancer research, biology.protein, Heterografts, Tumor Hypoxia, Female, GLUT1, medicine.symptom, Carcinogenesis |
| الوصف: | Hypoxia as well as metabolism are central hallmarks of cancer, and hypoxia-inducible factors (HIFs) and metabolic effectors are crucial elements in oxygen-compromised tumor environments. Knowledge of changes in the expression of metabolic proteins in response to HIF function could provide mechanistic insights into adaptation to hypoxic stress, tumorigenesis, and disease progression. We analyzed time-resolved alterations in metabolism-associated protein levels in response to different oxygen potentials across breast cancer cell lines. Effects on the cellular metabolism of both HIF-dependent and -independent processes were analyzed by reverse-phase protein array profiling and a custom statistical model. We revealed a strong induction of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA) as well as reduced glutamate-ammonia ligase (GLUL) protein levels across all cell lines tested as consistent changes upon hypoxia induction. Low GLUL protein levels were correlated with aggressive molecular subtypes in breast cancer patient data sets and also with hypoxic tumor regions in a xenograft mouse tumor model. Moreover, low GLUL expression was associated with poor survival in breast cancer patients and with high HIF-1α-expressing patient subgroups. Our data reveal time-resolved changes in the regulation of metabolic proteins under oxygen-deprived conditions and elucidate GLUL as a strong responder to HIFs and the hypoxic environment. |
| تدمد: | 1535-3907 1535-3893 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9360fa9072116372abfd5f21c5ddb59aTest https://doi.org/10.1021/acs.jproteome.8b00944Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....9360fa9072116372abfd5f21c5ddb59a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15353907 15353893 |
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