The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
RETRACTED: The mTORC1/S6K1 Pathway Regulates Glutamine Metabolism through the eIF4B-Dependent Control of c-Myc Translation
Open accessAbstract
Growth-promoting signaling molecules including the mammalian Target of Rapamycin Complex 1 (mTORC1) drive the metabolic reprogramming of cancer cells required to support their biosynthetic needs for rapid growth and proliferation [1]. Glutamine is catabolyzed to α-ketoglutarate (αKG), a TCA cycle intermediate, through two deamination reactions, the first requiring glutaminase (GLS) to generate glutamate, and the second reaction occurring via glutamate dehydrogenase (GDH) or transaminases [2]. Activation of the mTORC1 pathway was previously shown to promote the anaplerotic entry of glutamine to the tricarboxylic acid (TCA) cycle via GDH. Moreover, mTORC1 activation also stimulates the uptake of glutamine, but the mechanism is unknown [3]. It is generally thought that rates of glutamine utilization are limited by mitochondrial uptake via GLS, suggesting that in addition to GDH, mTORC1 could regulate GLS. Here, we demonstrate that mTORC1 positively regulates GLS and flux through this enzyme. We show that mTORC1 controls GLS levels through the S6K1-dependent regulation of c-Myc (Myc). Molecularly, S6K1 enhances Myc translation efficiency by modulating the phosphorylation of eukaryotic initiation factor eIF4B, which is critical to unwind its structured 5’ untranslated region (5’UTR). Finally, our data show that the pharmacological inhibition of GLS is a promising target in pancreatic cancers expressing low levels of PTEN.
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Cites
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Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1
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Cited by
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
mTOR signalling and cellular metabolism are mutual determinants in cancer
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mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle
Ben-Sahra, I., Hoxhaj, G., Ricoult, S. J. H., Asara, J. M., & Manning, B. D. (2016) · Science · doi:10.1126/science.aad0489 · Cited by 795
MYC: Connecting selective transcriptional control to global RNA production
Kress, T. R., Sabò, A., & Amati, B. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3984 · Cited by 521
Metadata
- Authors
- Csibi, A., Lee, G., Yoon, S.-O., Tong, H., Ilter, D., Elia, I., Fendt, S.-M., Roberts, T. M., & Blenis, J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 24
- Issue
- 19
- Pages
- 2274-2280
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2085386632
- Cited by
- 256
- References
- 29
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
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- CoChat. (2026). Citation check: RETRACTED: The mTORC1/S6K1 Pathway Regulates Glutamine Metabolism through the eIF4B-Dependent Control of c-Myc Translation. https://app.cochat.ai/papers/10.1016/j.cub.2014.08.007
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- Csibi, A., Lee, G., Yoon, S.-O., Tong, H., Ilter, D., Elia, I., Fendt, S.-M., Roberts, T. M., & Blenis, J. (2014). RETRACTED: The mTORC1/S6K1 Pathway Regulates Glutamine Metabolism through the eIF4B-Dependent Control of c-Myc Translation. Current Biology. https://doi.org/10.1016/j.cub.2014.08.007
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