The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma
Open accessAbstract
Here, we propose a new model for understanding the Warburg effect in tumor metabolism. Our hypothesis is that epithelial cancer cells induce the Warburg effect (aerobic glycolysis) in neighboring stromal fibroblasts. These cancer-associated fibroblasts, then undergo myo-fibroblastic differentiation, and secrete lactate and pyruvate (energy metabolites resulting from aerobic glycolysis). Epithelial cancer cells could then take up these energy-rich metabolites and use them in the mitochondrial TCA cycle, thereby promoting efficient energy production (ATP generation via oxidative phosphorylation), resulting in a higher proliferative capacity. In this alternative model of tumorigenesis, the epithelial cancer cells instruct the normal stroma to transform into a wound-healing stroma, providing the necessary energy-rich micro-environment for facilitating tumor growth and angiogenesis. In essence, the fibroblastic tumor stroma would directly feed the epithelial cancer cells, in a type of host-parasite relationship. We have termed this new idea the "Reverse Warburg Effect." In this scenario, the epithelial tumor cells "corrupt" the normal stroma, turning it into a factory for the production of energy-rich metabolites. This alternative model is still consistent with Warburg's original observation that tumors show a metabolic shift towards aerobic glycolysis. In support of this idea, unbiased proteomic analysis and transcriptional profiling of a new model of cancer-associated fibroblasts (caveolin-1 (Cav-1) deficient stromal cells), shows the upregulation of both (1) myo-fibroblast markers and (2) glycolytic enzymes, under normoxic conditions. We validated the expression of these proteins in the fibroblastic stroma of human breast cancer tissues that lack stromal Cav-1. Importantly, a loss of stromal Cav-1 in human breast cancers is associated with tumor recurrence, metastasis, and poor clinical outcome. Thus, an absence of stromal Cav-1 may be a biomarker for the "Reverse Warburg Effect," explaining its powerful predictive value.
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CAFs serve as a metabolic source of nutrients for cancer cells by generating energy-rich metabolites such as ketones, lactate, and pyruvate that support mitochondrial oxidative phosphorylation in adjacent tumor cells.
“In addition to structural remodeling, CAFs serve as metabolic source of nutrients for cancer cells. Tumor cells induce oxidative stress in adjacent fibroblasts, triggering the production of reactive oxygen species (ROS) [42,43,44]. This ROS burden initiates autophagic processes in fibroblasts, leading to the generation of energy-rich metabolites such as ketones, lactate, and pyruvate. These”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [45]
CAFs secrete lactate, which tumor cells use as a metabolic fuel by incorporating it into oxidative phosphorylation in mitochondria, supporting high proliferation rates (the reverse Warburg effect).
“Moreover, CAFs reportedly secrete lactate, which tumor cells can use as a metabolic fuel by incorporating it into oxidative phosphorylation (OXPHOS) in the mitochondria, thereby supporting their high proliferation rates. This phenomenon is known as the “reverse Warburg effect”.270”
From Drug repurposing for cancer therapy (2024) · cites this paper as [270]
Cites
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
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · see citing works
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820 · see citing works
Caveolin-1 Null Mice Are Viable but Show Evidence of Hyperproliferative and Vascular Abnormalities
Razani, B., Engelman, J. A., Wang, X., Schubert, W., Zhang, X. L., Marks, C. B., Macaluso, F., Russell, R. G., Li, M., Pestell, R. G., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105408200 · Cited by 1,163 · see citing works
Self-citationCancer as an overhealing wound: an old hypothesis revisited
Schäfer, M., & Werner, S. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2455 · Cited by 947 · see citing works
Lu, H., Forbes, R. A., & Verma, A. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202487200 · Cited by 839 · see citing works
The development of the DIGE system: 2D fluorescence difference gel analysis technology
Marouga, R., David, S., & Hawkins, E. (2005) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-005-3126-3 · Cited by 641 · see citing works
Razani, B., Zhang, X. L., Bitzer, M., von Gersdorff, G., Böttinger, E. P., & Lisanti, M. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008340200 · Cited by 640 · see citing works
Self-citationOh, P., Li, Y., Yu, J., Dürr, E., Krasinska, K. M., Carver, L. A., Testa, J. E., & Schnitzer, J. E. (2004) · Nature · doi:10.1038/nature02580 · Cited by 475 · see citing works
Benita, Y., Kikuchi, H., Smith, A. D., Zhang, M. Q., Chung, D. C., & Xavier, R. J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp425 · Cited by 469 · see citing works
RhoGDI: multiple functions in the regulation of Rho family GTPase activities
Dovas, A., & Couchman, J. (2005) · Biochemical Journal · doi:10.1042/bj20050104 · Cited by 414 · see citing works
Mesker, W. E., Junggeburt, J. M. C., Szuhai, K., de Heer, P., Morreau, H., Tanke, H. J., & Tollenaar, R. A. E. M. (2007) · Analytical Cellular Pathology · doi:10.1155/2007/175276 · Cited by 354 · see citing works
Witkiewicz, A. K., Dasgupta, A., Sotgia, F., Mercier, I., Pestell, R. G., Sabel, M. S., Kleer, C. G., Brody, J. R., & Lisanti, M. P. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080873 · Cited by 283 · see citing works
Self-citationCaveolin-1 Is Essential for Liver Regeneration
Fernandez-Rojo, M. A., Albor, C. V., Ingelmo‐Torres, M., Nixon, S. J., Ferguson, C., Kurzchalia, T. V., Tebar, F., Enrich, C., Parton, R. G., & Pol, A. (2006) · Science · doi:10.1126/science.1130773 · Cited by 271 · see citing works
Correlation of high lactate levels in head and neck tumors with incidence of metastasis.
Walenta, S., Salameh, A., Lyng, H., Evensen, J. F., Mitze, M., Rofstad, E. K., & Mueller‐Klieser, W. (1997) · Europe PMC (PubMed Central) · Cited by 251 · see citing works
Wang, C., Li, Z., Lu, Y., Du, R., Katiyar, S., Yang, J., Fu, M., Leader, J. E., Quong, A. A., Novikoff, P. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603363103 · Cited by 208 · see citing works
Self-citationCyclin D1 Determines Mitochondrial Function InVivo
Sakamaki, T., Casimiro, M. C., Ju, X., Quong, A. A., Katiyar, S., Liu, M., Jiao, X., Li, A., Zhang, X., Lu, Y., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02074-05 · Cited by 184 · see citing works
Self-citationHuman Skin Keloid Fibroblasts Display Bioenergetics of Cancer Cells
Vincent, A. S., Phan, T. T., Mukhopadhyay, A., Lim, H. Y., Halliwell, B. B., & Wong, K. P. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701107 · Cited by 170 · see citing works
Galdo, F. D., Sotgia, F., de Almeida, C. J., Jasmin, J.-F., Musick, M., Lisanti, M. P., & Jiménez, S. A. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23791 · Cited by 164 · see citing works
Self-citationSchneiderhan, W., Scheler, M., Holzmann, K.-H., Marx, M., Gschwend, J. E., Buchholz, M. A., Gress, T. M., Seufferlein, T. T. W., Adler, G., & Oswald, F. (2009) · Gut · doi:10.1136/gut.2009.181412 · Cited by 162 · see citing works
Endothelial cell response to lactate: Implication of PAR modification of VEGF
Kumar, V. B. S., Viji, R. I., Kiran, M. S., & Sudhakaran, P. R. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20955 · Cited by 143 · see citing works
Vizio, D. D., Morello, M., Sotgia, F., Pestell, R. G., Freeman, M. R., & Lisanti, M. P. (2009) · Cell Cycle · doi:10.4161/cc.8.15.9116 · Cited by 137 · see citing works
Self-citationGlycolysis and methylaminoisobutyrate uptake in rat-1 cells transfected with ras or myc oncogenes.
Racker, E., Resnick, R. J., & Feldman, R. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.11.3535 · Cited by 135 · see citing works
Galdo, F. D., Lisanti, M. P., & Jiménez, S. A. (2008) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e3283103d27 · Cited by 132 · see citing works
Self-citationMesker, W. E., Liefers, G., Junggeburt, J. M. C., et al. (2009) · PubMed · doi:10.3233/clo-2009-0478 · Cited by 131 · see citing works
Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer
Witkiewicz, A. K., Dasgupta, A., Nguyen, K., Liu, C., Kovatich, A. J., Schwartz, G. F., Pestell, R. G., Sotgia, F., Rui, H., & Lisanti, M. P. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.11.8874 · Cited by 128 · see citing works
Self-citationBelAiba, R. S., Djordjevic, T., Bonello, S., Flügel, D., Hess, J., Kietzmann, T., & Görlach, A. (2004) · Biological Chemistry · doi:10.1515/bc.2004.019 · Cited by 126 · see citing works
Sotgia, F., Galdo, F. D., Casimiro, M. C., Bonuccelli, G., Mercier, I., Whitaker‐Menezes, D., Daumer, K. M., Zhou, J., Wang, C., Katiyar, S., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080658 · Cited by 115 · see citing works
Self-citationFunctional Proteomics: Examining the Effects of Hypoxia on the Cytotrophoblast Protein Repertoire
Hoang, V. M., Foulk, R. A., Clauser, K. R., Burlingame, A. L., Gibson, B. W., & Fisher, S. J. (2001) · Biochemistry · doi:10.1021/bi0023910 · Cited by 115 · see citing works
Origin of carcinoma associated fibroblasts
Haviv, I., Polyák, K., Qiu, W., Hu, M., & Campbell, I. (2009) · Cell Cycle · doi:10.4161/cc.8.4.7669 · Cited by 114 · see citing works
Phan, T. T., Lim, I. J., Chan, S. Y., Tan, E.-K., Lee, S.-T., & Longaker, M. T. (2004) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000114087.46566.eb · Cited by 107 · see citing works
In vitro anti-fibrotic activities of herbal compounds and herbs
Hu, Q., Noor, M., Wong, Y. F., et al. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp245 · Cited by 100 · see citing works
Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers
Bagley (2009) · International Journal of Oncology · doi:10.3892/ijo_00000187 · Cited by 82 · see citing works
Custodis, F., EBERL, M., Kilter, H., Böhm, M., & Laufs, U. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.04.005 · Cited by 81 · see citing works
Phan, T. T., Sun, L. J., Bay, B., Chan, S. Y., & Lee, S.-T. (2003) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000030630.72836.32 · Cited by 73 · see citing works
Injectable poly-L-lactic acid for cosmetic enhancement: Learning from the European experience
Butterwick, K. J., & Lowe, N. J. (2009) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2008.11.881 · Cited by 66 · see citing works
Liao, S., Zhao, X., Han, Y., Zhang, J., Wang, L., Xia, L., Zhao, K., Zheng, Y., Guo, M., & Chen, G. (2009) · PROTEOMICS · doi:10.1002/pmic.200800922 · Cited by 64 · see citing works
Joseph, P., Lei, Y., Whong, W., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109373200 · Cited by 56 · see citing works
Towards a new “stromal-based” classification system for human breast cancer prognosis and therapy
Witkiewicz, A. K., Casimiro, M. C., Dasgupta, A., et al. (2009) · Cell Cycle · doi:10.4161/cc.8.11.8544 · Cited by 52 · see citing works
Self-citationPhan, T. T., Lim, I. J., Sun, L. J., et al. (2003) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2003.08.008 · Cited by 48 · see citing works
Differential expression of annexins I and II in normal and malignant human mammary epithelial cells
Schwartz‐Albiez, R., Koretz, K., Möller, P., & Wirl, G. (1993) · Differentiation · doi:10.1111/j.1432-0436.1993.tb00635.x · Cited by 41 · see citing works
Kotake‐Nara, E., & Saida, K. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.06.026 · Cited by 27 · see citing works
A Metabolic Push to Proliferate
Brasaemle, D. (2006) · Science · doi:10.1126/science.1133253 · Cited by 25 · see citing works
Caveolin-1 and Liver Regeneration: Role in Proliferation and Lipogenesis
Frank, P. G., & Lisanti, M. P. (2007) · Cell Cycle · doi:10.4161/cc.6.2.3722 · Cited by 25 · see citing works
Self-citationUrinary calcium excretion in the monitoring of bone metastases from prostatic carcinoma
Francini, G., Petrioli, R., Gonnelli, S., Correale, P., Pozzessere, D., Marsili, S., Montagnani, A., Lucani, B., Rossi, S., Monaco, R. D., et al. (2001) · Cancer · doi:10.1002/1097-0142(20010915)92:6 · Cited by 15 · see citing works
Lei, Y., Chen, J., & Wu, Z. (2002) · Teratogenesis Carcinogenesis and Mutagenesis · doi:10.1002/tcm.10034 · Cited by 15 · see citing works
Influence of quercetin and x-ray on collagen synthesis of cultured human keloid-derived fibroblasts.
Long, X., Zeng, X., Zhang, F., et al. (2006) · PubMed · Cited by 14 · see citing works
Expression of the α-Fetoprotein Gene in Human Breast Cancer
Esteban, C., Terrier, P., Lafarge‐Frayssinet, C., et al. (1996) · Tumor Biology · doi:10.1159/000217992 · Cited by 11 · see citing works
Flagged first, then by citations
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The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366 · 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
The return of metabolism: biochemistry and physiology of the pentose phosphate pathway
Stincone, A., Prigione, A., Cramer, T., Wamelink, M. M. C., Campbell, K., Cheung, E., Olin‐Sandoval, V., Grüning, N., Krüger, A., Tauqeer Alam, M., et al. (2015) · Biological Reviews · doi:10.1111/brv.12140 · Cited by 1,576 · see citing works
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505 · see citing works
Self-citationLactate Metabolism in Human Lung Tumors
Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.019 · Cited by 1,343 · see citing works
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265 · see citing works
Metabolic heterogeneity in human lung tumors
Hensley, C. T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.034 · Cited by 1,138 · see citing works
Fong, M. Y., Zhou, W., Liu, L., Alontaga, A. Y., Chandra, M., Ashby, J., Chow, A., O’Connor, S. T. F., Li, S., Chin, A. R., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3094 · Cited by 1,118 · see citing works
Metabolic Interactions in the Tumor Microenvironment
Lyssiotis, C. A., & Kimmelman, A. C. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.003 · Cited by 853 · see citing works
“The phenomenon, whereby CAFs take in glucose and release lactate to cancer cells, has been coined the “reverse Warburg effect” [40, 55].”
BackgroundCancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth
Shiga, K., Hara, M., Nagasaki, T., Sato, T., Takahashi, H., & Takeyama, H. (2015) · Cancers · doi:10.3390/cancers7040902 · Cited by 774 · see citing works
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S., & Zhou, H. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00641-0 · Cited by 773 · see citing works
Metabolic Reprogramming: the Emerging Concept and Associated Therapeutic Strategies
Yoshida, G. J. (2015) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-015-0221-y · Cited by 716 · see citing works
Stromal cells in tumor microenvironment and breast cancer
Mao, Y., Keller, E. T., Garfield, D. H., Shen, K., & Wang, J. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9415-3 · Cited by 671 · see citing works
Metabolites and the Tumour Microenvironment: From Cellular Mechanisms to Systemic Metabolism
Elia, I., & Haigis, M. C. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00317-z · Cited by 651 · see citing works
Cancer-associated fibroblasts: from basic science to anticancer therapy
Yang, D., Liu, J., Qian, H., & Zhuang, Q. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01013-0 · Cited by 572 · see citing works
A history of exploring cancer in context
Maman, S., & Witz, I. P. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0006-7 · Cited by 502 · see citing works
Choosing between glycolysis and oxidative phosphorylation: a tumor’s dilemma?
Jose, C., Bellance, N., & Rossignol, R. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.012 · Cited by 518 · see citing works
Cancer-associated adipocytes: key players in breast cancer progression
Wu, Q., Li, B., Li, Z., Li, J., Sun, S., & Sun, S. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0778-6 · Cited by 462 · see citing works
3D cell culture systems modeling tumor growth determinants in cancer target discovery
Thoma, C. R., Zimmermann, M., Agarkova, I., Kelm, J. M., & Krek, W. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.03.001 · Cited by 478 · see citing works
Drug repurposing for cancer therapy
Xia, Y., Sun, M., Huang, H., & Jin, W.-L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01808-1 · Cited by 443 · see citing works
“270 Tumor metabolic reprogramming also plays a pivotal role in shaping the immune response, speci fi cally antitumor immunity.”
BackgroundMartinez-Outschoorn, U. E., Lisanti, M. P., & Sotgia, F. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.01.005 · Cited by 423 · see citing works
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Chen, Y.-J., Mahieu, N. G., Huang, X., Singh, M., Crawford, P. A., Johnson, S. L., Gross, R. W., Schaefer, J., & Patti, G. J. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2172 · Cited by 326 · see citing works
Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H(+) symporters
Marchiq, I., & Pouysségur, J. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1307-x · Cited by 300 · see citing works
Metabolic reprogramming in the tumor microenvironment of liver cancer
Lin, J., Rao, D., Zhang, M., & Gao, Q. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01527-8 · Cited by 251 · see citing works
Martinez-Outschoorn, U. E., Pavlides, S., Howell, A., Pestell, R. G., Tanowitz, H. B., Sotgia, F., & Lisanti, M. P. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.01.023 · Cited by 248 · see citing works
Self-citationWitkiewicz, A. K., Whitaker-Menezes, D., Dasgupta, A., Philp, N. J., Lin, Z., Gandara, R., Sneddon, S., Martinez-Outschoorn, U. E., Sotgia, F., & Lisanti, M. P. (2012) · Cell Cycle · doi:10.4161/cc.11.6.19530 · Cited by 239 · see citing works
Self-citationCapparelli, C., Chiavarina, B., Whitaker-Menezes, D., Pestell, T. G., Pestell, R. G., Hulit, J., Andò, S., Howell, A., Martinez-Outschoorn, U. E., Sotgia, F., et al. (2012) · Cell Cycle · doi:10.4161/cc.21884 · Cited by 221 · see citing works
Self-citationRattigan, Y. I., Patel, B. B., Ackerstaff, E., Sukenick, G., Koutcher, J. A., Glod, J. W., & Banerjee, D. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.11.014 · Cited by 196 · see citing works
Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer
Kennedy, K. M., Scarbrough, P. M., Ribeiro, A., Richardson, R., Yuan, H., Sonveaux, P., Landon, C. D., Chi, J.-T., Pizzo, S., Schroeder, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075154 · Cited by 190 · see citing works
Martinez-Outschoorn, U. E., Pestell, R. G., Howell, A., Tykocinski, M. L., Nagajyothi, F., Machado, F. S., Tanowitz, H. B., Sotgia, F., & Lisanti, M. P. (2011) · Cell Cycle · doi:10.4161/cc.10.24.18487 · Cited by 157 · see citing works
The metabolic landscape of lung cancer: New insights in a disturbed glucose metabolism
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Extracellular vesicles are independent metabolic units with asparaginase activity
Iraci, N., Gaude, E., Leonardi, T., Costa, A. S. H., Cossetti, C., Peruzzotti-Jametti, L., Bernstock, J. D., Saini, H. K., Gelati, M., Vescovi, A. L., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2422 · Cited by 134 · see citing works
Obre, E., & Rossignol, R. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.12.008 · Cited by 137 · see citing works
Sun, K., Tang, S., Hou, Y., Xi, L., Chen, Y., Yin, J., Peng, M., Zhao, M., Cui, X., & Liu, M. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.02.025 · Cited by 138 · see citing works
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Mercier, I., Camacho, J., Titchen, K., Gonzales, D. M., Quann, K., Bryant, K. G., Molchansky, A., Milliman, J. N., Whitaker-Menezes, D., Sotgia, F., et al. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.03.017 · Cited by 96 · see citing works
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Sun, W. Y., Kim, H. M., Jung, W.-H., & Koo, J. S. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0915-8 · Cited by 77 · see citing works
Amoedo, N. D., Obre, E., & Rossignol, R. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.02.005 · Cited by 76 · see citing works
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
“These metabolites are shuttled to adjacent tumor cells and support mitochondrial oxidative phosphorylation, thereby sustaining tumor cell growth and bioenergetic demands [42–45].”
Role of the tumor microenvironment in cancer hallmarks and targeted therapy (Review)
Naser, R., Fakhoury, I., El‑Fouani, A., Abi‑Habib, R., & El‑Sibai, M. (2022) · International Journal of Oncology · doi:10.3892/ijo.2022.5471 · Cited by 61 · see citing works
Fotsitzoudis, C., Koulouridi, A., Messaritakis, I., Konstantinidis, T., Gouvas, N., Tsiaoussis, J., & Souglakos, J. (2022) · Cancers · doi:10.3390/cancers14184394 · Cited by 46 · see citing works
Jo, S.-H., Kim, D. E., Clocchiatti, A., & Dotto, G. P. (2016) · Oncotarget · doi:10.18632/oncotarget.11227 · Cited by 13 · see citing works
Hypoxic microenvironment in cancer: role in metabolic reprogramming
Sureka, N., Maheshwari, R., Agravat, A., Singhal, S., Zaman, S., Rishi, B., Siraj, F., Zaheer, S., & Misra, A. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1771365 · Cited by 11 · see citing works
Prognostic value of glycolysis markers in pancreatic cancer: A systematic review and meta-analysis
Wang, C., Xu, R., Song, J., Chen, Y., Yin, X., Ruze, R., & Xu, Q. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1004850 · Cited by 6 · see citing works
Self-citation
- Authors
- Pavlides, S., Whitaker-Menezes, D., Castello-Cros, R., Flomenberg, N., Witkiewicz, A. K., Frank, P. G., Casimiro, M. C., Wang, C., Fortina, P., Addya, S., Pestell, R. G., Martinez-Outschoorn, U. E., Sotgia, F., & Lisanti, M. P.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Sotgia, Federica
- Lisanti, Michael P.
- ORCID
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2009-12
- Volume
- 8
- Issue
- 23
- Pages
- 3984-4001
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2127675410
- Cited by
- 1,391
- References
- 48
- Citations by year
- 2026: 79 · 2025: 75 · 2024: 86 · 2023: 111 · 2022: 117 · 2021: 113 · 2020: 129 · 2019: 107 · 2018: 81 · 2017: 93 · 2016: 89 · 2015: 72 · 2014: 79 · 2013: 51 · 2012: 45
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cell Cycle (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Cancer Institute (R01CA107382, R01CA120876, R01CA086072, R01CA080250, R01CA075503, R01CA098779, R01CA070896, P30CA056036)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR055660)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- reverse Warburg effect, Warburg effect, aerobic glycolysis, cancer-associated fibroblasts, tumor stroma, myofibroblast differentiation, lactate secretion, pyruvate, mitochondrial TCA cycle, oxidative phosphorylation, caveolin-1, breast cancer, tumor microenvironment, tumor recurrence, metastasis, biomarkers, tumor-stroma interactions
- MeSH terms
- Animals, Breast Neoplasms, Female, Fibroblasts, Glycolysis, Humans, L-Lactate Dehydrogenase, Pyruvate Kinase, Up-Regulation, Stromal Cells, Annexins, Mice, Knockout, Tenascin, Proteomics, Caveolin 1, Mice
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