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Glutamine Deprivation Induces Abortive S-Phase Rescued by Deoxyribonucleotides in K-Ras Transformed Fibroblasts
Open accessAbstract
BACKGROUND: Oncogene activation plays a role in metabolic reprogramming of cancer cells. We have previously shown that K-ras transformed fibroblasts have a stronger dependence on glycolysis and a reduced oxidative phosphorylation ability as compared to their normal counterparts. Another metabolic adaptation of cancer cells, that has long been established, is their propensity to exhibit increased glutamine consumption, although the effects induced by glutamine deprivation on cancer cells are still controversial. METHODOLOGY AND PRINCIPAL FINDINGS: Here, by using nutritional perturbations and molecular physiology, we show that reduction or complete depletion of glutamine availability in K-ras transformed fibroblasts causes a strong decrease of proliferation ability and a slower re-entry of synchronized cells into the cell cycle. The reduced proliferation is accompanied by sustained expression of cyclin D and E, abortive S phase entrance and is dependent on Ras signalling deregulation, since it is rescued by expression of a dominant negative guanine nucleotide exchange factor. The growth potential of transformed cells as well as the ability to execute the G(1) to S transition is restored by adding the four deoxyribonucleotides, indicating that the arrest of proliferation of K-ras transformed cells induced by glutamine depletion is largely due to a reduced supply of DNA in the presence of signalling pathways promoting G(1) to S transition. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that the differential effects of glutamine and glucose on cell viability are not a property of the transformed phenotype per se, but rather depend on the specific pathway being activated in transformation. For instance, myc-overexpressing cells have been reported to die under glutamine depletion and not under glucose shortage, while the opposite holds for ras-transformed fibroblasts as shown in this paper. These different responses of transformed cells to nutritional stress should be taken into account when designing anti-cancer therapies that aim to exploit metabolic differences between normal and transformed cells.
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“Accordingly, glutamine levels have been shown to be rate-limiting for cell cycle progression, and glutamine deprivation leads to cell cycle arrest in the S-phase in certain cellular contexts (Fontenelle and Henderson, 1969; Gaglio et al., 2009).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Gaglio et al., 2009
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“Accordingly, glutamine levels have been shown to be rate-limiting for cell cycle progression, and glutamine deprivation leads to cell cycle arrest in the S-phase in certain cellular contexts (Fontenelle and Henderson, 1969; Gaglio et al., 2009).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Gaglio et al., 2009
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Citations
Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622
The Rb/E2F pathway: expanding roles and emerging paradigms
Harbour, J. W., & Dean, D. C. (2000) · Genes & Development · doi:10.1101/gad.813200 · Cited by 1,153
Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F., Roberts, J. M., & Sherr, C. J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1571 · Cited by 1,142 · cited 10×
“Notably both Cdk2 and Cdk4 kinase complexes phosphorylate, during the G1 to S transition, pRb protein on Ser 795.”
BackgroundInfluentialPKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest
Liang, J., Zubovitz, J., Petrocelli, T., Kotchetkov, R., Connor, M. K., Han, K. C.-Z., Lee, J.-H., Ciarallo, S., Catzavelos, C., Beniston, R., et al. (2002) · Nature Medicine · doi:10.1038/nm761 · Cited by 952
Transforming p21 Mutants and c-Ets-2 Activate the Cyclin D1 Promoter through Distinguishable Regions
Albanese, C., Johnson, J., Watanabe, G., Eklund, N., Vu, D., Arnold, A., & Pestell, R. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.40.23589 · Cited by 802
Shin, I., Yakes, F. M., Rojo, F., Shin, N.-Y., Bakin, A. V., Baselga, J. M., & Arteaga, C. L. (2002) · Nature Medicine · doi:10.1038/nm759 · Cited by 797
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Items 101–166 of 166
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Kodama, M., Oshikawa, K., Shimizu, H., Yoshioka, S., Takahashi, M., Izumi, Y., Bamba, T., Tateishi, C., Tomonaga, T., Matsumoto, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15136-9 · Cited by 14
Wang, M., Guo, F., Hou, D.-S., Zhang, H., Chen, X.-T., Shen, Y., Guo, Z.-F., Zheng, Z.-F., Hu, Y., Du, P., et al. (2025) · Protein & Cell · doi:10.1093/procel/pwaf029 · Cited by 13
Prasad, A., Roy, A. C., Priya, K., Meena, R., & Ghosh, I. (2023) · 3 Biotech · doi:10.1007/s13205-023-03759-w · Cited by 14
Pandian, S. R. K., Deepak, V., Hariharan, N., & Sundar, K. (2014) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-014-9840-4 · Cited by 13
Gaglio, D., Valtorta, S., Ripamonti, M., Bonanomi, M., Damiani, C., Todde, S., Negri, A. S., Sanvito, F., Mastroianni, F., Campli, A. D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10470 · Cited by 15
Self-citationGlutamine Addiction of Cancer Cells
Desideri, E., & Ciriolo, M. R. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1932-1_8 · Cited by 11
Dihydroorotate dehydrogenase inhibition reveals metabolic vulnerability in chronic myeloid leukemia
Houshmand, M., Vitale, N., Orso, F., Cignetti, A., Molineris, I., Gaidano, V., Sainas, S., Giorgis, M., Boschi, D., Fava, C., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05028-9 · Cited by 12
Malakar, P., Singha, D., Choudhury, D., & Shukla, S. K. (2023) · Cell Cycle · doi:10.1080/15384101.2023.2260166 · Cited by 12
Metabotropic Glutamate Receptors in Cancer
Yu, L. J., Wall, B., Wangari‐Talbot, J., & Chen, S. (2017) · Springer eBooks · doi:10.1007/978-3-319-56170-7_9 · Cited by 13
Vadlakonda, L., Indracanti, M., Kalangi, S. K., Gayatri, B. M., Gajula, N. N., & Reddy, A. B. M. (2020) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-020-00566-5 · Cited by 11
Wilderman, A. S., Guo, Y., Divakaruni, A. S., Perkins, G. A., Zhang, L., Murphy, A. N., Taylor, S. S., & Insel, P. A. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.658153 · Cited by 11
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03758-0 · Cited by 13
Enzymatic depletion of circulating glutamine is immunosuppressive in cancers
Kumar, M., Leekha, A., Nandy, S., Kulkarni, R. S., Martinez-Paniagua, M. A., Sefat, K. M. S. R., Willson, R. C., & Varadarajan, N. (2024) · iScience · doi:10.1016/j.isci.2024.109817 · Cited by 10
Yang, T., Tian, Y., Yang, Y., Tang, M., Shi, M., Chen, Y. X., Yang, Z., & Chen, L. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114686 · Cited by 10
de Candia, P., Minopoli, G., Verga, V., Gargiulo, A., Vanoni, M., & Alberghina, L. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2010.12.047 · Cited by 10
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Shin, D. Y., Choi, S. H., Park, D. I., & Choi, Y. H. (2013) · Journal of Life Science · doi:10.5352/jls.2013.23.6.832 · Cited by 5
Qi, Y., Ma, N., & Zhang, J. (2023) · International Journal of Oncology · doi:10.3892/ijo.2023.5581 · Cited by 5
Li, X., Li, D., Li, J., Chen, Y., Cai, Z., & Tan, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411753 · Cited by 4
Robert, A., Crottès, D., Bourgeais, J., Guéguen, N., Chevrollier, A., Dumas, J., Servais, S., Domingo, I., Chadet, S., Sobilo, J., et al. (2024) · PLoS Biology · doi:10.1371/journal.pbio.3002854 · Cited by 5
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Regulating Mitochondrial Respiration in Cancer
Serafim, T. L., & Oliveira, P. J. (2014) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-1-4614-9545-1_3 · Cited by 3
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Robert, A., Crottès, D., Bourgeais, J., Guéguen, N., Chevrollier, A., Dumas, J., Servais, S., Domingo, I., Chadet, S., Sobilo, J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.31.564893 · Cited by 1
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House, R. J., Tovar, E. A., Essenburg, C. J., Dischinger, P. S., Ellis, A. E., Beddows, I., Sheldon, R. D., Lien, E. C., Graveel, C. R., & Steensma, M. R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.24.568339 · Cited by 1
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Thiagalingam, S. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9780511979811.012
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Mukhopadhyay, S. (2015) · CUNY Academic Works (City University of New York) · doi:10.13140/rg.2.1.4721.3848
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Bathe, O. F. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-408103-1.00014-5
Adegbesan, B. O. (2018) · Research Explorer (The University of Manchester)
Cell Metabolism in Cancer: An Energetic Switch
de Castro, I. P. (2019) · Learning materials in biosciences · doi:10.1007/978-3-030-11812-9_6 · Cited by 1
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Chen, J., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-898527/v1
Fanale, D., Incorvaia, L., Russo, A. D., Longo, V. D., & Mirisola, M. G. (2021) · UNIPA Springer series · doi:10.1007/978-3-030-56051-5_25
Mayor, S., & Hemalatha, A. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718064192.793555326
Immune Cell Metabolites as Fuel for Cancer Cells
Aggarwal, V., Rathod, S., Vashishth, K., & Upadhyay, A. (2022) · Springer eBooks · doi:10.1007/978-981-16-6226-3_6
Yousif, A., Ebeid, A., Kacsoh, B. Z., Bazzaro, M., & Chefetz, I. (2024) · Cells · doi:10.3390/cells13010094 · Cited by 1
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592747
Maurer, J., Mukherjee, P., Ta, N. L., Lee, D. C., Duraj, T., Henao, J., Kiebish, M., Cura, D. V., Herdocia, M., & Seyfried, T. N. (2025) · ONCOLOGIE · doi:10.1515/oncologie-2025-0238
Mauricio, A. B. (2014) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592783
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592771
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592780
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592750
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592765
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592756
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592774
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592759
Wang, L., Zhu, Z., Liang, Q., Tao, Y., Jin, G., Zhong, Y., Dai, J., Dai, R., Wang, Z., Chen, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21592762
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Study of tumor cell metabolism and its relationship with NK cell-mediated immunotherapy
Krzywińska, E. (2014) · theses.fr (ABES) · doi:10.70675/55685772z0acez4c8bzaf02z3edd2b0ef19f
Biochemical characterization of mTORC1 regulation by glutamine metabolism
Bodineau, C. (2020) · theses.fr (ABES) · doi:10.70675/9d5aaabdz81bdz4118zb3edze237bdd8dee0
Robert, A. (2023) · theses.fr (ABES) · doi:10.70675/32fe7e68z8cadz475dz9938ze92c0bee2f0a
Haider, J., Huang, X., Xu, C., & Leung, T. (2026) · Cells · doi:10.3390/cells15121116
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Metadata
- Authors
- Gaglio, D., Soldati, C., Vanoni, M., Alberghina, L., & Chiaradonna, F.
- Affiliations
- University of Milano-Bicocca (IT)
- Corresponding author
- Chiaradonna, Ferdinando
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-03-05
- Volume
- 4
- Issue
- 3
- Pages
- e4715
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2650790
- OpenAlex
- W2070710923
- Cited by
- 164
- References
- 60
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 12 · 2023: 9 · 2022: 21 · 2021: 11 · 2020: 10 · 2019: 16 · 2018: 6 · 2017: 12 · 2016: 9 · 2015: 12 · 2014: 14 · 2013: 8 · 2012: 6
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Fund for Astrophysical Research
- Regione Lombardia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- glutamine deprivation, deoxyribonucleotides, G1/S transition, Ras signaling, guanine nucleotide exchange factor, cell cycle arrest, cancer metabolism, metabolic reprogramming, nutritional stress, cell proliferation
- MeSH terms
- Animals, Cell Cycle, Cell Transformation, Neoplastic, Deoxyribonucleotides, Fibroblasts, Glutamine, Genes, ras, S Phase, 3T3 Cells, Cell Proliferation, Mice
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