The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target
Open accessAbstract
A handful of tumor-derived cell lines form the mainstay of cancer therapeutic development, yielding drugs with an impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics and more readily understand their clinical impact, we constructed a functional metabolic portrait of 46 independently derived breast cell lines. Our analysis of glutamine uptake and dependence identified a subset of triple-negative samples that are glutamine auxotrophs. Ambient glutamine indirectly supports environmental cystine acquisition via the xCT antiporter, which is expressed on one-third of triple-negative tumors in vivo. xCT inhibition with the clinically approved anti-inflammatory sulfasalazine decreases tumor growth, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“implying that xc− may constitute a therapeutic target in this setting [553, 554].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [553]
In the citing paper
“the pronounced addiction of triple-negative breast carcinoma to glutamine relates (at least in part) to its ability to drive cystine uptake via xc−, implying that xc− may constitute a therapeutic target in this setting [553, 554].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [553]
In the citing paper
“Consistent with this observation, glutamine starvation has been associated with impaired uptake of cystine through xCT and decreased intracellular glutathione levels62.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes
Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., Clark, L., Bayani, N., Coppé, J., Tong, F. K., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.008 · Cited by 3,224
Self-citationFatty acid synthase and the lipogenic phenotype in cancer pathogenesis
Menendez, J. A., & Lupu, R. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2222 · Cited by 2,941
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
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer
Prat, A., Parker, J. S., Karginova, O. A., Fan, C., Livasy, C., Herschkowitz, J. I., He, X., & Perou, C. M. (2010) · Breast Cancer Research · doi:10.1186/bcr2635 · Cited by 2,290
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001
Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy
Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., et al. (2009) · Cell · doi:10.1016/j.cell.2008.11.044 · Cited by 1,798
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293
Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy
Koppula, P., Zhuang, L., & Gan, B. (2020) · Protein & Cell · doi:10.1007/s13238-020-00789-5 · Cited by 2,640
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
Dixon, S. J., Patel, D. N., Welsch, M., Skouta, R., Lee, E. D., Hayano, M., Thomas, A. G., Gleason, C. E., Tatonetti, N. P., Slusher, B. S., et al. (2014) · eLife · doi:10.7554/elife.02523 · Cited by 2,088
Metadata
- Authors
- Timmerman, L. A., Holton, T., Yuneva, M., Louie, R. J., Padró, M., Daemen, A., Hu, M., Chan, D. A., Ethier, S. P., van ‘t Veer, L. J., Polyak, K., McCormick, F., & Gray, J. W.
- Affiliations
- University of California, San Francisco (US)
- San Francisco State University (US)
- Medical Research Council (GB)
- Novartis (China) (CN)
- Medical University of South Carolina (US)
- Oregon Health & Science University (US)
- Corresponding author
- Timmerman, Luika A.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 24
- Issue
- 4
- Pages
- 450-465
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3931310
- OpenAlex
- W2034530633
- Cited by
- 573
- References
- 61
- Citations by year
- 2026: 21 · 2025: 46 · 2024: 50 · 2023: 51 · 2022: 49 · 2021: 75 · 2020: 56 · 2019: 55 · 2018: 37 · 2017: 39 · 2016: 39 · 2015: 33 · 2014: 21
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of California, San Francisco
- National Cancer Institute (P50CA058207, U54CA112970)
- 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 › Biotechnology › Bacterial Cancer Therapy
- Keywords
- triple-negative breast cancer, glutamine addiction, glutamine uptake, sulfasalazine, therapeutic target, breast cancer cell lines, cancer metabolism, drug development
- MeSH terms
- Animals, Female, Glutamine, Glutathione, Humans, Prognosis, Gene Expression Regulation, Neoplastic, Reactive Oxygen Species, Disease Progression, Gene Expression Profiling, Amino Acid Transport System y+, RNA, Small Interfering, Cell Line, Tumor, Mice, Triple Negative Breast Neoplasms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
