Academic Journal
Disrupting the MYC-TFEB Circuit Impairs Amino Acid Homeostasis and Provokes Metabolic Anergy
| العنوان: | Disrupting the MYC-TFEB Circuit Impairs Amino Acid Homeostasis and Provokes Metabolic Anergy |
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| المؤلفون: | Fernandez M. R., Schaub F. X., Yang C., Li W., Yun S., Schaub S. K., Dorsey F. C., Liu M., Steeves M. A., Ballabio A., Tzankov A., Chen Z., Koomen J. M., Berglund A. E., Cleveland J. L. |
| المساهمون: | Fernandez, M. R., Schaub, F. X., Yang, C., Li, W., Yun, S., Schaub, S. K., Dorsey, F. C., Liu, M., Steeves, M. A., Ballabio, A., Tzankov, A., Chen, Z., Koomen, J. M., Berglund, A. E., Cleveland, J. L. |
| سنة النشر: | 2022 |
| المجموعة: | IRIS Università degli Studi di Napoli Federico II |
| مصطلحات موضوعية: | Amino Acid, Animal, Autophagy, Homeostasi, Human, Mice, Proteasome Endopeptidase Complex, Basic Helix-Loop-Helix Leucine Zipper Transcription Factor, Lysosome, Proto-Oncogene Proteins c-myc |
| الوصف: | MYC family oncoproteins are regulators of metabolic reprogramming that sustains cancer cell anabolism. Normal cells adapt to nutrient-limiting conditions by activating autophagy, which is required for amino acid (AA) homeostasis. Here we report that the autophagy pathway is suppressed by Myc in normal B cells, in premalignant and neoplastic B cells of Em-Myc transgenic mice, and in human MYC-driven Burkitt lymphoma. Myc suppresses autophagy by antagonizing the expression and function of transcription factor EB (TFEB), a master regulator of autophagy. Mechanisms that sustained AA pools in MYC-expressing B cells include coordinated induction of the proteasome and increases in AA transport. Reactivation of the autophagy-lysosomal pathway by TFEB disabled the malignant state by disrupting mitochondrial functions, proteasome activity, AA transport, and AA and nucleotide metabolism, leading to metabolic anergy, growth arrest, and apoptosis. This phenotype provides therapeutic opportunities to disable MYC-driven malignancies, including AA restriction and treatment with proteasome inhibitors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000783233900001; volume:82; issue:7; firstpage:1234; lastpage:1250; numberofpages:17; journal:CANCER RESEARCH; http://hdl.handle.net/11588/883838; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85128160937 |
| DOI: | 10.1158/0008-5472.CAN-21-1168 |
| الاتاحة: | http://hdl.handle.net/11588/883838 https://doi.org/10.1158/0008-5472.CAN-21-1168 |
| رقم الانضمام: | edsbas.EDFB829B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/0008-5472.CAN-21-1168 |
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