Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer
Open accessAbstract
Glutamine can play a critical role in cellular growth in multiple cancers. Glutamine‐addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Here, we have uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high‐invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients’ microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the activation of STAT3, a mediator of signaling pathways which regulates cancer hallmarks in invasive OVCA cells. Our findings suggest that a combined approach of targeting high‐invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting low‐invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.
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
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?
Some tumors predominantly use glutamine under hypoxia or conditions mimicking hypoxia such as electron transport chain inhibition through reductive carboxylation for biosynthetic needs.
“recent studies show that some tumors predominantly use glutamine under hypoxia or conditions mimicking hypoxia such as electron transport chain inhibition through reductive carboxylation for biosynthetic needs (Yang et al., 2014; Wise et al., 2008).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Yang et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383 · see citing works
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427 · see citing works
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 · see citing works
Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth
Nieman, K. M., Kenny, H. A., Penicka, C. V., Ladanyi, A., Buell-Gutbrod, R., Zillhardt, M. R., Romero, I. L., Carey, M. S., Mills, G. B., Hotamisligil, G. S., et al. (2011) · Nature Medicine · doi:10.1038/nm.2492 · Cited by 2,279 · see citing works
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 · see citing works
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 · see citing works
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990 · see citing works
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 · see citing works
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791 · see citing works
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 · see citing works
Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003428107 · Cited by 1,742 · see citing works
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
DeBerardinis, R. J., & Cheng, T. (2010) · Oncogene · doi:10.1038/onc.2009.358 · Cited by 1,365 · see citing works
Reductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328 · see citing works
JAK-STAT Signaling: From Interferons to Cytokines
Schindler, C., Levy, D. E., & Decker, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r700016200 · Cited by 1,263 · see citing works
Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells
Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.009 · Cited by 1,095 · see citing works
Self-citationMcCarty, K. S., MILLER, L. S., Cox, E. B., Konrath, J. G., & McCarty, K. S. (1985) · PubMed · Cited by 1,027 · see citing works
Function of Mitochondrial Stat3 in Cellular Respiration
Wegrzyn, J., Potla, R., Chwae, Y.-J., Sepuri, N. B. V., Zhang, Q., Koeck, T., Derecka, M., Szczepanek, K., Szelag, M., Gornicka, A., et al. (2009) · Science · doi:10.1126/science.1164551 · Cited by 1,014 · see citing works
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007 · see citing works
Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis
Nomura, D. K., Long, J. Z., Niessen, S., Hoover, H. S., Ng, S.-W., & Cravatt, B. F. (2010) · Cell · doi:10.1016/j.cell.2009.11.027 · Cited by 1,002 · see citing works
MYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities
Dang, C. V., Le, A., & Gao, P. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0889 · Cited by 934 · see citing works
Enhanced DNA-Binding Activity of a Stat3-Related Protein in Cells Transformed by the Src Oncoprotein
Yu, C.-L., Meyer, D. J., Campbell, G. S., Larner, A. C., Carter-Su, C., Schwartz, J., & Jove, R. (1995) · Science · doi:10.1126/science.7541555 · Cited by 931 · see citing works
Levy, D., & Lee, C.-K. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15650 · Cited by 925 · see citing works
Paraneoplastic thrombocytosis in ovarian cancer
Stone, R. L., Nick, A. M., McNeish, I. A., Balkwill, F., Han, H. D., Bottsford-Miller, J., Rupaimoole, R., Armaiz-Pena, G. N., Pecot, C. V., Coward, J., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1110352 · Cited by 812 · see citing works
Self-citationGarcia, R., Bowman, T. L., Niu, G., Yu, H., Minton, S., Muro‐Cacho, C., Cox, C. E., Falcone, R., Fairclough, R., Parsons, S. J., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204349 · Cited by 747 · see citing works
Levy, D. E., & Lee, C.-K. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215650 · Cited by 734 · see citing works
Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery
Landen, C. N., Chávez‐Reyes, A., Bucana, C. D., Schmandt, R. E., Deavers, M. T., Lopez‐Berestein, G., & Sood, A. K. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0530 · Cited by 674 · see citing works
Self-citationSignal Transducer and Activator of Transcription‐3, Inflammation, and Cancer
Aggarwal, B. B., Kunnumakkara, A. B., Harikumar, K. B., Gupta, S. R., Tharakan, S. T., Koca, C., Dey, S., & Sung, B. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04911.x · Cited by 652 · see citing works
STAT proteins: novel molecular targets for cancer drug discovery
Turkson, J., & Jove, R. (2000) · Oncogene · doi:10.1038/sj.onc.1204086 · Cited by 643 · see citing works
Evidence for an Alternative Glycolytic Pathway in Rapidly Proliferating Cells
Heiden, M. G. V., Locasale, J. W., Swanson, K. D., Sharfi, H., Heffron, G. J., Amador‐Noguez, D., Christofk, H. R., Wagner, G., Rabinowitz, J. D., Asara, J. M., et al. (2010) · Science · doi:10.1126/science.1188015 · Cited by 635 · see citing works
Chung, J., Uchida, E., Grammer, T. C., & Blenis, J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.11.6508 · Cited by 620 · see citing works
The mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4
Csibi, A., Fendt, S.-M., Li, C., Poulogiannis, G., Choo, A. Y., Chapski, D. J., Jeong, S. M., Dempsey, J. M., Parkhitko, A., Morrison, T., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.023 · Cited by 586 · see citing works
Oncogenic K‐Ras decouples glucose and glutamine metabolism to support cancer cell growth
Gaglio, D., Metallo, C. M., Gameiro, P. A., Hiller, K., Danna, L. S., Balestrieri, C., Alberghina, L., Stephanopoulos, G., & Chiaradonna, F. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.56 · Cited by 492 · see citing works
Pyruvate carboxylase is required for glutamine-independent growth of tumor cells
Cheng, T., Sudderth, J., Yang, C., Mullen, A. R., Jin, E. S., Matés, J. M., & DeBerardinis, R. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016627108 · Cited by 475 · see citing works
Metabolic flux and the regulation of mammalian cell growth
Locasale, J. W., & Cantley, L. C. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.07.014 · Cited by 449 · see citing works
Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis
Silva, C. M. (2004) · Oncogene · doi:10.1038/sj.onc.1208159 · Cited by 400 · see citing works
Kunkel, M., Reichert, T. E., Benz, P. M., Lehr, H., Jeong, J., Wieand, S., Bartenstein, P., Wagner, W., & Whiteside, T. L. (2003) · Cancer · doi:10.1002/cncr.11159 · Cited by 390 · see citing works
Metabolic reprogramming in cancer: Unraveling the role of glutamine in tumorigenesis
Daye, D., & Wellen, K. E. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.02.002 · Cited by 375 · see citing works
Garcia, R., Yu, C., Hudnall, A. M., Catlett, R., Nelson, K. L., Smithgall, T. E., Fujita, D. J., Ethier, S. P., & Jove, R. (1997) · PubMed · Cited by 369 · see citing works
Focal adhesion size uniquely predicts cell migration
Kim, D., & Wirtz, D. (2012) · The FASEB Journal · doi:10.1096/fj.12-220160 · Cited by 358 · see citing works
A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction
Demaria, M., Giorgi, C., Lebiedzińska, M., Esposito, G., D’Angeli, L., Bartoli, A., Gough, D. J., Turkson, J., Levy, D., Watson, C., et al. (2010) · Aging · doi:10.18632/aging.100232 · Cited by 277 · see citing works
Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells
Burke, W. M., Jin, X., Lin, H.-J. L., Huang, M., Liu, R., Reynolds, R. K., & Lin, J. (2001) · Oncogene · doi:10.1038/sj.onc.1204990 · Cited by 269 · see citing works
Tedeschi, P. M., Markert, E. K., Gounder, M. K., Lin, H., Dvorzhinski, D., Dolfi, S. C., Chan, L. L.-Y., Qiu, J., DiPaola, R. S., Hirshfield, K. M., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.393 · Cited by 261 · see citing works
Merritt, W. M., Lin, Y. G., Spannuth, W. A., Fletcher, M. S., Kamat, A. A., Han, L. Y., Landen, C. N., Jennings, N., Geest, K. D., Langley, R. R., et al. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn024 · Cited by 257 · see citing works
Self-citationDuan, Z., Foster, R., Bell, D. A., Mahoney, J., Wolak, K. E., Vaidya, A. P., Hampel, C., Lee, H., & Seiden, M. V. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0861 · Cited by 247 · see citing works
Glutaminolysis: Supplying carbon or nitrogen or both for cancer cells?
Dang, C. V. (2010) · Cell Cycle · doi:10.4161/cc.9.19.13302 · Cited by 245 · see citing works
Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle
Arvizo, R. R., Saha, S., Wang, E., Robertson, J. D., Bhattacharya, R., & Mukherjee, P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214547110 · Cited by 237 · see citing works
Src activation by β-adrenoreceptors is a key switch for tumour metastasis
Armaiz-Pena, G. N., Allen, J. K., Cruz, A., Stone, R. L., Nick, A. M., Lin, Y. G., Han, L. Y., Mangala, L. S., Villares, G. J., Vivas-Mejia, P., et al. (2013) · Nature Communications · doi:10.1038/ncomms2413 · Cited by 212 · see citing works
Self-citationGlucose deprivation activates a metabolic and signaling amplification loop leading to cell death
Graham, N. A., Tahmasian, M., Kohli, B., Komisopoulou, E., Zhu, M. X., Vivanco, I., Teitell, M. A., Wu, H., Ribas, A., Lo, R. S., et al. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.20 · Cited by 207 · see citing works
Gohil, V. M., Sheth, S., Nilsson, R., Wojtovich, A. P., Lee, J. H., Perocchi, F., Chen, W., Clish, C., Ayata, C., Brookes, P., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1606 · Cited by 191 · see citing works
Klopp, A. H., Zhang, Y., Solley, T., Amaya-Manzanares, F., Marini, F., Andreeff, M., Debeb, B., Woodward, W., Schmandt, R., Broaddus, R., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1916 · Cited by 178 · see citing works
Glutamine: pleiotropic roles in tumor growth and stress resistance
Shanware, N. P., Mullen, A. R., DeBerardinis, R. J., & Abraham, R. T. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0731-9 · Cited by 176 · see citing works
A physical sciences network characterization of non-tumorigenic and metastatic cells
Agus, D. B., Alexander, J. F., Arap, W., Ashili, S., Aslan, J. E., Austin, R. H., Backman, V., Bethel, K. J., Bonneau, R., Chen, W., et al. (2013) · Scientific Reports · doi:10.1038/srep01449 · Cited by 171 · see citing works
Singh, M., Zaino, R. J., Filiaci, V. L., et al. (2007) · Gynecologic Oncology · doi:10.1016/j.ygyno.2007.03.042 · Cited by 165 · see citing works
Gaglio, D., Soldati, C., Vanoni, M., Alberghina, L., & Chiaradonna, F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004715 · Cited by 164 · see citing works
Yu, X., Kennedy, R. H., & Liu, S. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212321200 · Cited by 146 · see citing works
Sandulache, V. C., Ow, T. J., Pickering, C. R., Frederick, M. J., Zhou, G., Fokt, I., Davis‐Malesevich, M., Priebe, W., & Myers, J. N. (2011) · Cancer · doi:10.1002/cncr.25868 · Cited by 143 · see citing works
Hao, W., Chang, C.-P. B., Tsao, C.-C., & Xu, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.084194 · Cited by 138 · see citing works
Yue, P., Zhang, X., Paladino, D., Sengupta, B., Ahmad, S., Holloway, R. W., Ingersoll, S. B., & Turkson, J. (2011) · Oncogene · doi:10.1038/onc.2011.409 · Cited by 135 · see citing works
Gough, D. J., Koetz, L., & Levy, D. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083395 · Cited by 133 · see citing works
Global Profiling Strategies for Mapping Dysregulated Metabolic Pathways in Cancer
Benjamin, D. I., Cravatt, B. F., & Nomura, D. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.09.013 · Cited by 130 · see citing works
Role of Glutamine in Cancer: Therapeutic and Imaging Implications: FIGURE 1.
Rajagopalan, K. N., & DeBerardinis, R. J. (2011) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.084244 · Cited by 120 · see citing works
Komurov, K., Tseng, J., Muller, M., Seviour, E. G., Moss, T. J., Yang, L., Nagrath, D., & Ram, P. T. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.25 · Cited by 117 · see citing works
Self-citationCaneba, C. A., Bellancé, N., Yang, L., Pabst, L., & Nagrath, D. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00151.2012 · Cited by 94 · see citing works
Self-citationStoichiometry of STAT3 and Mitochondrial Proteins
Phillips, D. J., Reilley, M. J., Aponte, A. M., Wang, G., Boja, E. S., Guček, M., & Balaban, R. S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.152652 · Cited by 93 · see citing works
Subcellular Localization of p27kip1 Expression Predicts Poor Prognosis in Human Ovarian Cancer
Rosen, D. G., Yang, G. S., Cai, K. Q., Bast, R. C., Gershenson, D. M., Silva, E. G., & Liu, J. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.632.11.2 · Cited by 73 · see citing works
Self-citationKataoka, K., Kim, D. J., Carbajal, S., Clifford, J. L., & DiGiovanni, J. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn061 · Cited by 65 · see citing works
Liu, Z., Jia, X., Duan, Y., Xiao, H., Sundqvist, K., Permert, J., & Wang, F. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.23786 · Cited by 57 · see citing works
Matsuo, K., Nishimura, M., Komurov, K., et al. (2013) · Gynecologic Oncology · doi:10.1016/j.ygyno.2013.10.027 · Cited by 38 · see citing works
Effect of glutamine on glutathione, IGF-I, and TGF-β1
Johnson, A. T., Kaufmann, Y., Luo, S., et al. (2003) · Journal of Surgical Research · doi:10.1016/s0022-4804(03)00083-0 · Cited by 33 · see citing works
Staging recurrent ovarian cancer with 18FDG PET/CT
Dragosavac, S., Derchain, S., Caserta, N. M. G., et al. (2012) · Oncology Letters · doi:10.3892/ol.2012.1075 · Cited by 32 · see citing works
Ovarian cancer: Stat3, RhoA and IGF-IR as therapeutic targets
Gest, C., Mirshahi, P., Li, H., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.11.026 · Cited by 31 · see citing works
Russo, P., Arzani, D., Trombino, S., et al. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.042952 · Cited by 25 · see citing works
Kornfeld, S., Goupille, C., Vibet, S., Chevalier, S., Pinet, A., Lebeau, J., Tranquart, F., Bougnoux, P., Martel, E., Maurin, A., et al. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr274 · Cited by 23 · see citing works
Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific.
Zhai, Q. “., Rosen, D. G., Lu, K. H., & Liu, J. (2008) · PubMed Central · Cited by 22 · see citing works
Self-citationProgenitor Cell Mobilization from Extramedullary Organs
Kolonin, M. G. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-943-3_20 · Cited by 15 · see citing works
Recapitulating cancer cell invasion in vitro
Kim, D., & Wirtz, D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103983108 · Cited by 11 · see citing works
(1998) · Pure Amsterdam UMC · doi:10.1002/(sici)1097-0142(19980701)83:1 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
Zhao, H., Yang, L., Baddour, J., Achreja, A., Bernard, V., Moss, T., Marini, J. C., Tudawe, T., Seviour, E. G., San Lucas, F. A., et al. (2016) · eLife · doi:10.7554/elife.10250 · Cited by 927 · see citing works
Self-citationGlutaminolysis: A Hallmark of Cancer Metabolism
Yang, L., Venneti, S., & Nagrath, D. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044546 · Cited by 859 · see citing works
Self-citationTumor glycolysis, an essential sweet tooth of tumor cells
Paul, S., Ghosh, S., & Kumar, S. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.09.007 · Cited by 449 · see citing works
Emerging roles and therapeutic value of exosomes in cancer metastasis
Wu, M., Wang, G., Hu, W., Yao, Y., & Yu, X.-F. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0964-8 · Cited by 140 · see citing works
Salimian Rizi, B., Caneba, C., Nowicka, A., Nabiyar, A. W., Liu, X., Chen, K., Klopp, A., & Nagrath, D. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1337 · Cited by 98 · see citing works
Self-citationGlutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism
Cacace, A., Sboarina, M., Vazeille, T., & Sonveaux, P. (2017) · Oncogene · doi:10.1038/onc.2016.364 · Cited by 76 · see citing works
Hoerner, C. R., Chen, V. J., & Fan, A. C. (2019) · Kidney Cancer · doi:10.3233/kca-180043 · Cited by 68 · see citing works
Using Machine Learning to Measure Relatedness Between Genes: A Multi-Features Model
Wang, Y., Yang, S., Zhao, J., Du, W., Liang, Y., Wang, C., Zhou, F., Tian, Y., & Ma, Q. (2019) · Scientific Reports · doi:10.1038/s41598-019-40780-7 · Cited by 26 · see citing works
Exploiting metabolic vulnerabilities after anti-VEGF antibody therapy in ovarian cancer
Glassman, D., Kim, M. S., Spradlin, M., Badal, S., Taki, M., Bhattacharya, P., Dutta, P., Kingsley, C. V., Foster, K. I., Animasahun, O., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106020 · Cited by 15 · see citing works
Self-citation
- Authors
- Yang, L., Moss, T., Mangala, L. S., Marini, J., Zhao, H., Wahlig, S., Armaiz‐Pena, G., Jiang, D., Achreja, A., Win, J., Roopaimoole, R., Rodriguez‐Aguayo, C., Mercado‐Uribe, I., Lopez‐Berestein, G., Liu, J., Tsukamoto, T., Sood, A. K., Ram, P. T., & Nagrath, D.
- Affiliations
- Rice University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Baylor College of Medicine (US)
- Johns Hopkins University (US)
- Corresponding author
- Nagrath, Deepak
- ORCID
- Venue
- Molecular Systems Biology
- Published
- 2014-05-01
- Volume
- 10
- Issue
- 5
- Pages
- 728-728
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC4188042
- OpenAlex
- W2159550690
- Cited by
- 326
- References
- 79
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 34 · 2023: 46 · 2022: 32 · 2021: 33 · 2020: 30 · 2019: 27 · 2018: 28 · 2017: 22 · 2016: 22 · 2015: 17 · 2014: 5
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Rice Research Repository (Rice University) (submittedVersion, cc-by)
- Funders
- Ken Kennedy institute for Information technology at Rice University
- John and Ann Doerr Fund
- University of Texas MD Anderson Cancer Center
- NIH (CA016672, P50 CA083639, P50 CA098258, U54 CA151668, UH2 TR000943‐01)
- CPRIT (RP110595)
- Ovarian Cancer Research Fund, Inc.
- Blanton‐Davis Ovarian Cancer Research Program
- Gilder Foundation
- 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 metabolism, ovarian cancer, tumor invasion, glutamine addiction, glutaminolysis, TCA cycle, STAT3 activation, prognostic factors, tumor bioenergetics, tumor metabolic reprogramming
- MeSH terms
- Cell Cycle, Energy Metabolism, Female, Glutamine, Humans, Ovarian Neoplasms, Prognosis, Signal Transduction, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cell Proliferation
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
