Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Open accessAbstract
Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism to the transformed phenotype remains unknown. Here we show that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell. The internalized protein undergoes proteolytic degradation, yielding amino acids including glutamine that can enter central carbon metabolism. Accordingly, the dependence of Ras-transformed cells on free extracellular glutamine for growth can be suppressed by the macropinocytic uptake of protein. Consistent with macropinocytosis representing an important route of nutrient uptake in tumours, its pharmacological inhibition compromises the growth of Ras-transformed pancreatic tumour xenografts. These results identify macropinocytosis as a mechanism by which cancer cells support their unique metabolic needs and point to the possible exploitation of this process in the design of anticancer therapies.
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?
Albumin uptake by cancer cells especially occurs in nutrient-deprived states and is regulated by mTORC1.
“This especially occurs in nutrient‐deprived states and is regulated by mammalian target of rapamycin complex 1 (mTORC1), controlling protein synthesis.94”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [94]
The passage on glutamine deprivation (section labeled Abstract; page unavailable) reports that albumin supplementation helped Ras-transformed cells proliferate when glutamine was low, and that the benefit depended on macropinocytosis. It does not show that albumin uptake occurs especially during nutrient deprivation. Searches for mTORC1 and mammalian target of rapamycin found no passage supporting regulation of uptake by mTORC1 or the associated protein-synthesis claim. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPDAC cells harboring KRAS* rely on increased levels of macropinocytosis for nutrient salvaging to sustain uncontrolled cell growth.
“PDAC cells harboring KRAS∗ rely on increased levels of macropinocytosis for nutrient salvaging to sustain uncontrolled cell growth.14”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [14]
Macropinocytosis is a nutrient salvage process that supports oncogenic growth.
“a nutrient salvage process that supports oncogenic growth.14”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [14]
PDAC cells utilize macropinocytosis to obtain amino acids through uptake and degradation of albumin and collagen.
“PDAC cells utilize macropinocytosis to obtain amino acids through the uptake and degradation of albumin and collagen230–232”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [230]
PDAC cells can utilize macropinocytosis to obtain proline from CAF-produced collagen.
“PDAC cells can utilize macropinocytosis to obtain proline from CAF produced collagen230.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [230]
Exosomes supply amino acids to nutrient-deprived cancer cells via a macropinocytosis-like mechanism that does not depend on oncogenic Kras signaling, including in wild-type and activated Kras-expressing pancreatic cancer cells.
“Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling.”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Commisso et al., 2013
Macropinocytosis of circulating proteins (especially albumin) can supply amino acids to nutrient-deprived cancer cells.
“Recent studies have shown that macropinocytosis of circulating proteins (especially albumin) could supply amino acids to nutrient-deprived cancer cells (Commisso et al., 2013).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Commisso et al., 2013
Exosomes act as source of metabolites in a manner similar to macropinocytosis in Kras expressing pancreatic cancer cells.
“These results suggested that exosomes themselves might be acting as source of metabolites in a manner similar to macropinocytosis observed recently in Kras expressing pancreatic cancer cells (Commisso et al., 2013).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Commisso et al., 2013
Expression of mutant Ras or c-Src provides a mechanism to recover free amino acids through lysosomal degradation of extracellular proteins.
“expression of mutant Ras or c-Src alleles provides cells with a mechanism that allows them to recover free amino acids through the lysosomal degradation of extracellular proteins”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Commisso et al., 2013
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
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · 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
Self-citationReductive 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
Self-citationComplete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue
Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H., & Goeddel, D. V. (1983) · Nature · doi:10.1038/302033a0 · Cited by 997 · see citing works
Bar-Sagi, D., & Feramisco, J. R. (1986) · Science · doi:10.1126/science.3090687 · Cited by 734 · see citing works
Self-citationPharmacological Inhibition of Endocytic Pathways: Is It Specific Enough to Be Useful?
Ivanov, A. I. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-178-9_2 · Cited by 605 · 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
Self-citationGLUTAMINE METABOLISM IN LYMPHOCYTES: ITS BIOCHEMICAL, PHYSIOLOGICAL AND CLINICAL IMPORTANCE
Newsholme, E. A., Crabtree, B., & Ardawi, M. S. M. (1985) · Quarterly Journal of Experimental Physiology · doi:10.1113/expphysiol.1985.sp002935 · Cited by 465 · see citing works
West, M. A. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.109.6.2731 · Cited by 451 · see citing works
Nolan-Stevaux, O., Lau, J., Truitt, M. L., Chu, G. C., Hebrok, M., Fernández-Zapico, M., & Hanahan, D. (2009) · Genes & Development · doi:10.1101/gad.1753809 · Cited by 398 · see citing works
Stehle, G., Sinn, H., Wunder, A., Schrenk, H. H., Stewart, J. C. M., Hartung, G., Maier-Borst, W., & Heene, D. L. (1997) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(97)00015-2 · Cited by 305 · see citing works
High Precision Isotope Ratio Monitoring Techniques in Mass Spectrometry
Brand, W. A. (1996) · Journal of Mass Spectrometry · doi:10.1002/(sici)1096-9888(199603)31:3 · Cited by 299 · see citing works
Accurate Assessment of Amino Acid Mass Isotopomer Distributions for Metabolic Flux Analysis
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2007) · Analytical Chemistry · doi:10.1021/ac0708893 · Cited by 257 · see citing works
Wagner, M., Greten, F. R., Weber, C. K., Koschnick, S., Mattfeldt, T., Deppert, W., Kern, H. F., Adler, G., & Schmid, R. M. (2001) · Genes & Development · doi:10.1101/gad.184701 · Cited by 204 · see citing works
Differential Activation of the Rac Pathway by Ha-Ras and K-Ras
Walsh, A. B., & Bar‐Sagi, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010573200 · Cited by 173 · see citing works
Self-citationSubstrate balances across colonic carcinomas in humans.
Holm, E., Hagmüller, E., Staedt, U., Schlickeiser, G., Günther, H.-J., Leweling, H., TOKUS, M., & Kollmar, H. B. (1995) · PubMed · Cited by 169 · 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
Glutamine homeostasis and mitochondrial dynamics
Matés, J. M., Segura, J. A., Campos-Sandoval, J. A., Lobo, C., Alonso, L., Alonso, F. J., & Márquez, J. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.03.003 · Cited by 157 · see citing works
Aoki, K., Yoshida, T., Sügimura, T., & Terada, M. (1995) · PubMed · Cited by 151 · see citing works
A Unique Platform for H-Ras Signaling Involving Clathrin-independent Endocytosis
Porat‐Shliom, N., Kloog, Y., & Donaldson, J. G. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-08-0841 · Cited by 123 · see citing works
Knowles, M. A., & Williamson, M. P. (1993) · PubMed · Cited by 112 · see citing works
v-Src induces constitutive macropinocytosis in rat fibroblasts
Veithen, A., Cupers, P., Baudhuin, P., & Courtoy, P. J. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.8.2005 · Cited by 103 · see citing works
Role of Src‐family kinases in formation and trafficking of macropinosomes
Kasahara, K., Nakayama, Y., Sato, I., Ikeda, K., Hoshino, M., Endo, T., & Yamaguchi, N. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20931 · Cited by 101 · see citing works
Src Triggers Circular Ruffling and Macropinocytosis at the Apical Surface of Polarized MDCK Cells
Mettlen, M., Platek, A., van der Smissen, P., Carpentier, S., Amyere, M., Lanzetti, L., de Diesbach, P., Tyteca, D., & Courtoy, P. (2006) · Traffic : the International Journal of Intracellular Transport · doi:10.1111/j.1600-0854.2006.00412.x · Cited by 92 · see citing works
Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase
Wu, M., Arimura, G. K., & Yunis, A. A. (1978) · International Journal of Cancer · doi:10.1002/ijc.2910220615 · Cited by 77 · see citing works
Dynamics of Pre-replicative Complex Assembly
Tsakraklides, V., & Bell, S. P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.072504 · Cited by 71 · see citing works
A novel methodology for the investigation of intracellular proteolytic processing in intact cells
Reis, R. C. M., Sorgine, M. H. F., & Coelho‐Sampaio, T. (1998) · European Journal of Cell Biology · doi:10.1016/s0171-9335(98)80061-7 · Cited by 55 · see citing works
Hirai, H., & Varmus, H. E. (1990) · Genes & Development · doi:10.1101/gad.4.12b.2342 · Cited by 29 · see citing works
Rapid and large-scale method to detect K-ras gene mutations in tumor samples
Lopez‐Crapez, E., Chypre, C., Saavedra, J., Marchand, J., & Grenier, J. (1997) · Clinical Chemistry · doi:10.1093/clinchem/43.6.936 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The biology <b>,</b> function <b>,</b> and biomedical applications of exosomes
Kalluri, R., & LeBleu, V. S. (2020) · Science · doi:10.1126/science.aau6977 · Cited by 10,770 · see citing works
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · see citing works
Self-citationCancer nanomedicine: progress, challenges and opportunities
Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.108 · Cited by 5,873 · see citing works
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013 · see citing works
Metabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740 · see citing works
Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer
Kamerkar, S., LeBleu, V. S., Sugimoto, H., Yang, S., Ruivo, C. F., Melo, S. A., Lee, J. J., & Kalluri, R. (2017) · Nature · doi:10.1038/nature22341 · Cited by 2,639 · see citing works
Ryan, D. P., Hong, T. S., & Bardeesy, N. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1404198 · Cited by 2,348 · see citing works
Understanding the Intersections between Metabolism and Cancer Biology
Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,316 · see citing works
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
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982 · see citing works
Cancer metabolism: looking forward
Martínez‐Reyes, I., & Chandel, N. S. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00378-6 · Cited by 1,852 · see citing works
Every step of the way: integrins in cancer progression and metastasis
Hamidi, H., & Ivaska, J. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0038-z · Cited by 1,493 · see citing works
Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics
Rennick, J. J., Johnston, A. P. R., & Parton, R. G. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00858-8 · Cited by 1,500 · see citing works
The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418 · see citing works
Self-citationMetabolic pathways promoting cancer cell survival and growth
Boroughs, L. K., & DeBerardinis, R. J. (2015) · Nature Cell Biology · doi:10.1038/ncb3124 · Cited by 1,459 · see citing works
Hypoalbuminemia: Pathogenesis and Clinical Significance
Soeters, P. B., Wolfe, R. R., & Shenkin, A. (2019) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1451 · Cited by 1,448 · see citing works
Lipid metabolic reprogramming in cancer cells
Beloribi‐Djefaflia, S., Vasseur, S., & Guillaumond, F. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.49 · Cited by 1,392 · see citing works
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321 · see citing works
Mitochondrial metabolism and cancer
Porporato, P. E., Filigheddu, N., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2017) · Cell Research · doi:10.1038/cr.2017.155 · Cited by 1,292 · see citing works
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272 · see citing works
Metabolic regulation of cell growth and proliferation
Zhu, J., & Thompson, C. B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0123-5 · Cited by 1,106 · see citing works
Self-citationPancreatic stellate cells support tumour metabolism through autophagic alanine secretion
Sousa, C. M., Biancur, D. E., Wang, X., Halbrook, C. J., Sherman, M. H., Zhang, L., Kremer, D., Hwang, R. F., Witkiewicz, A. K., Ying, H., et al. (2016) · Nature · doi:10.1038/nature19084 · Cited by 1,122 · see citing works
Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer
Tiriac, H., Belleau, P., Engle, D. D., Plenker, D., Deschênes, A., Somerville, T. D. D., Froeling, F. E. M., Burkhart, R. A., Denroche, R. E., Jang, G.-H., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0349 · Cited by 1,092 · see citing works
Drugging the ‘undruggable’ cancer targets
Dang, C. V., Reddy, E. P., Shokat, K. M., & Soucek, L. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.36 · Cited by 927 · 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
Targeting Autophagy in Cancer: Recent Advances and Future Directions
Amaravadi, R. K., Kimmelman, A. C., & Debnath, J. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0292 · Cited by 928 · see citing works
The lysosome as a cellular centre for signalling, metabolism and quality control
Lawrence, R. E., & Zoncu, R. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0244-7 · Cited by 920 · see citing works
Kamphorst, J. J., Nofal, M., Commisso, C., Hackett, S. R., Lu, W., Grabocka, E., Vander Heiden, M. G., Miller, G., Drebin, J. A., Bar-Sagi, D., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2211 · Cited by 893 · 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
Autophagy and Tumor Metabolism
Kimmelman, A. C., & White, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.004 · Cited by 826 · see citing works
Lieu, E. L., Nguyen, T. A., Rhyne, S., & Kim, J. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0375-3 · Cited by 827 · see citing works
Glutamine Metabolism in Cancer: Understanding the Heterogeneity
Cluntun, A. A., Lukey, M. J., Cerione, R. A., & Locasale, J. W. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.01.005 · Cited by 796 · see citing works
Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism
Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., et al. (2015) · Nature · doi:10.1038/nature14587 · Cited by 799 · see citing works
Recent insights into the function of autophagy in cancerPreprint
Amaravadi, R. K., Kimmelman, A. C., & White, E. (2016) · Genes & Development · doi:10.1101/gad.287524.116 · Cited by 810 · see citing works
Hydrocarbon-Stapled Peptides: Principles, Practice, and Progress
Walensky, L. D., & Bird, G. H. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm4011675 · Cited by 803 · see citing works
An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma
Hakimi, A. A., Reznik, E., Lee, C., Creighton, C. J., Brannon, A. R., Luna, A., Aksoy, B. A., Liu, E. M., Shen, R., Lee, W., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.004 · Cited by 791 · see citing works
Generation and testing of clinical-grade exosomes for pancreatic cancer
Mendt, M. C., Kamerkar, S., Sugimoto, H., McAndrews, K. M., Wu, C.-C., Gagea, M., Yang, S., Blanko, E. V. R., Peng, Q., Ma, X., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.99263 · Cited by 795 · see citing works
Insight into nanoparticle cellular uptake and intracellular targeting
Yameen, B., Choi, W. I., Vilos, C., Swami, A., Shi, J., & Farokhzad, O. C. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.06.038 · Cited by 789 · see citing works
Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer
Davidson, S. M., Papagiannakopoulos, T., Olenchock, B. A., Heyman, J. E., Keibler, M. A., Luengo, A., Bauer, M. R., Jha, A. K., O’Brien, J. P., Pierce, K. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.007 · Cited by 737 · see citing works
Self-citationRole of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer
Buscail, L., Bournet, B., & Cordelier, P. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0245-4 · Cited by 721 · see citing works
Hypoxia and Metabolic Adaptation of Cancer Cells
Eales, K. L., Hollinshead, K. E. R., & Tennant, D. A. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.50 · Cited by 724 · see citing works
Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer
Bryant, K. L., Stalnecker, C. A., Zeitouni, D., Klomp, J. E., Peng, S., Tikunov, A. P., Gunda, V., Pierobon, M., Waters, A. M., George, S. D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0368-8 · Cited by 692 · see citing works
Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response
Olson, O. C., & Joyce, J. A. (2015) · Nature reviews. Cancer · doi:10.1038/nrc4027 · Cited by 703 · see citing works
Yang, C., Ko, B., Hensley, C. T., Jiang, L., Wasti, A. T., Kim, J., Sudderth, J., Calvaruso, M. A., Lumata, L., Mitsche, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.025 · Cited by 679 · see citing works
Hosios, A. M., Hecht, V. C., Danai, L. V., Johnson, M. O., Rathmell, J. C., Steinhauser, M. L., Manalis, S. R., & Vander Heiden, M. G. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.02.012 · Cited by 641 · see citing works
Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine
Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651 · see citing works
Self-citationKRAS: feeding pancreatic cancer proliferation
Bryant, K. L., Mancias, J. D., Kimmelman, A. C., & Der, C. J. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.12.004 · Cited by 675 · see citing works
Autophagy, Metabolism, and Cancer
White, E., Mehnert, J. M., & Chan, C. S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0490 · Cited by 669 · see citing works
The Lysosome as a Regulatory Hub
Perera, R. M., & Zoncu, R. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125125 · Cited by 664 · see citing works
Mayers, J. R., Wu, C. H., Clish, C. B., Kraft, P., Torrence, M. E., Fiske, B. P., Yuan, C., Bao, Y., Townsend, M. K., Tworoger, S. S., et al. (2014) · Nature Medicine · doi:10.1038/nm.3686 · Cited by 652 · see citing works
Self-citationUnraveling the mysteries of serum albumin—more than just a serum protein
Merlot, A. M., Kalinowski, D. S., & Richardson, D. R. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00299 · Cited by 643 · see citing works
Modulating the therapeutic response of tumours to dietary serine and glycine starvation
Maddocks, O. D. K., Athineos, D., Cheung, E. C., Lee, P., Zhang, T., van den Broek, N. J. F., Mackay, G. M., Labuschagne, C. F., Gay, D., Kruiswijk, F., et al. (2017) · Nature · doi:10.1038/nature22056 · Cited by 603 · see citing works
Mechanisms and Implications of Metabolic Heterogeneity in Cancer
Kim, J., & DeBerardinis, R. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.013 · Cited by 606 · see citing works
Cantor, J. R., Abu-Remaileh, M., Kanarek, N., Freinkman, E., Gao, X., Louissaint, A., Lewis, C. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.03.023 · Cited by 611 · see citing works
Sullivan, M. R., Danai, L. V., Lewis, C. A., Chan, S. H., Gui, D. Y., Kunchok, T., Dennstedt, E. A., Vander Heiden, M. G., & Muir, A. (2019) · eLife · doi:10.7554/elife.44235 · Cited by 588 · see citing works
Harnessing albumin as a carrier for cancer therapies
Hoogenboezem, E. N., & Duvall, C. L. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.07.011 · Cited by 615 · see citing works
Disrupting proton dynamics and energy metabolism for cancer therapy
Parks, S. K., Chiche, J., & Pouysségur, J. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3579 · Cited by 613 · see citing works
Tissue of origin dictates branched-chain amino acid metabolism in mutant <i>Kras</i> -driven cancers
Mayers, J. R., Torrence, M. E., Danai, L. V., Papagiannakopoulos, T., Davidson, S. M., Bauer, M. R., Lau, A. N., Ji, B. W., Dixit, P. D., Hosios, A. M., et al. (2016) · Science · doi:10.1126/science.aaf5171 · Cited by 582 · see citing works
Self-citationComprehensive quantification of fuel use by the failing and nonfailing human heart
Murashige, D., Jang, C., Neinast, M., Edwards, J. J., Cowan, A., Hyman, M. C., Rabinowitz, J. D., Frankel, D. S., & Arany, Z. (2020) · Science · doi:10.1126/science.abc8861 · Cited by 580 · see citing works
Self-citationUnderstanding cachexia as a cancer metabolism syndrome
Porporato, P. E. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.3 · Cited by 562 · see citing works
Targeting glutamine metabolism as a therapeutic strategy for cancer
Jin, J., Byun, J., Choi, Y., & Park, K. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-00971-9 · Cited by 574 · see citing works
Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets
Park, J. H., Pyun, W. Y., & Park, H. W. (2020) · Cells · doi:10.3390/cells9102308 · Cited by 558 · see citing works
PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells
Israelsen, W. J., Dayton, T. L., Davidson, S. M., Fiske, B. P., Hosios, A. M., Bellinger, G., Li, J., Yu, Y., Sasaki, M., Horner, J. W., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.025 · Cited by 549 · see citing works
Self-citationGenetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527 · see citing works
The dose threshold for nanoparticle tumour delivery
Ouyang, B., Poon, W., Zhang, Y.-N., Lin, Z. P., Kingston, B. R., Tavares, A. J., Zhang, Y., Chen, J., Valic, M. S., Syed, A. M., et al. (2020) · Nature Materials · doi:10.1038/s41563-020-0755-z · Cited by 518 · see citing works
One-carbon metabolism in cancer
Newman, A. C., & Maddocks, O. D. K. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.118 · Cited by 509 · see citing works
New aspects of amino acid metabolism in cancer
Vettore, L. A., Westbrook, R. L., & Tennant, D. A. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0620-5 · Cited by 503 · see citing works
Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment
Ackerman, D., & Simon, M. C. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.06.001 · Cited by 495 · see citing works
Emerging Roles for Branched-Chain Amino Acid Metabolism in Cancer
Sivanand, S., & Heiden, M. G. V. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.011 · Cited by 488 · see citing works
Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma
Grossberg, A. J., Chu, L. C. H., Deig, C. R., Fishman, E. K., Hwang, W. L., Maitra, A., Marks, D. L., Mehta, A., Nabavizadeh, N., Simeone, D. M., et al. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21626 · Cited by 491 · see citing works
Autophagy in cancer metastasis
Mowers, E. E., Sharifi, M. N., & Macleod, K. F. (2016) · Oncogene · doi:10.1038/onc.2016.333 · Cited by 476 · see citing works
Wyant, G., Abu-Remaileh, M., Wolfson, R. L., Chen, W. W., Freinkman, E., Danai, L. V., Heiden, M. V. V., & Sabatini, D. (2017) · Cell · doi:10.1016/j.cell.2017.09.046 · Cited by 434 · see citing works
Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis
Green, C. R., Wallace, M., Divakaruni, A. S., Phillips, S. A., Murphy, A. N., Ciaraldi, T. P., & Metallo, C. M. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.1961 · Cited by 471 · see citing works
Self-citationThe utilization of extracellular proteins as nutrients is suppressed by mTORC1
Palm, W., Park, Y., Wright, K., Pavlova, N. N., Tuveson, D. A., & Thompson, C. B. (2015) · Cell · doi:10.1016/j.cell.2015.06.017 · Cited by 457 · see citing works
Self-citationAspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours
Garcia-Bermudez, J., Baudrier, L., La, K., Zhu, X. G., Fidelin, J., Sviderskiy, V. O., Papagiannakopoulos, T., Molina, H., Snuderl, M., Lewis, C. A., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0118-z · Cited by 442 · see citing works
Yang, L., Achreja, A., Yeung, T.-L., Mangala, L. S., Jiang, D., Han, C., Baddour, J., Marini, J. C., Ni, J., Nakahara, R., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.011 · Cited by 433 · see citing works
Activated fibroblasts in cancer: Perspectives and challenges
Caligiuri, G., & Tuveson, D. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.015 · Cited by 431 · see citing works
Daemen, A., Peterson, D., Sahu, N., McCord, R., Du, X., Liu, B., Kowanetz, K., Hong, R., Moffat, J., Gao, M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501605112 · Cited by 398 · see citing works
Olivares, O., Mayers, J. R., Gouirand, V., Torrence, M. E., Gicquel, T., Borge, L., Lac, S., Roques, J., Lavaut, M.-N., Berthezène, P., et al. (2017) · Nature Communications · doi:10.1038/ncomms16031 · Cited by 413 · see citing works
Therapeutic strategies to target RAS-mutant cancers
Ryan, M. B., & Corcoran, R. B. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0105-0 · Cited by 420 · see citing works
Metabolism of pancreatic cancer: paving the way to better anticancer strategies
Qin, C., Yang, G., Yang, J., Ren, B., Wang, H., Chen, G., Zhao, F., You, L., Wang, W., & Zhao, Y. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01169-7 · Cited by 415 · see citing works
Mitochondria as biosynthetic factories for cancer proliferation
Ahn, C. S., & Metallo, C. M. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0128-2 · Cited by 399 · see citing works
Self-citationEmploying Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer
Halbrook, C. J., & Lyssiotis, C. A. (2017) · Cancer Cell · doi:10.1016/j.ccell.2016.12.006 · Cited by 394 · see citing works
Qiu, B., Ackerman, D., Sanchez, D. J., Li, B., Ochocki, J. D., Grazioli, A., Bobrovnikova-Marjon, E., Diehl, J. A., Keith, B., & Simon, M. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1507 · Cited by 394 · see citing works
Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
Bertero, T., Oldham, W. M., Grasset, E. M., Bourget, I., Boulter, E., Pisano, S., Hofman, P., Bellvert, F., Meneguzzi, G., Bulavin, D. V., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.012 · Cited by 393 · see citing works
Nutrient acquisition strategies of mammalian cells
Palm, W., & Thompson, C. B. (2017) · Nature · doi:10.1038/nature22379 · Cited by 388 · see citing works
Self-citationRecent progress in targeted delivery vectors based on biomimetic nanoparticles
Chen, L., Hong, W., Ren, W., Xu, T., Qian, Z., & He, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00631-2 · Cited by 388 · see citing works
Metabolic Pathways Regulating Colorectal Cancer Initiation and Progression
La Vecchia, S., & Sebastián, C. (2020) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.05.018 · Cited by 349 · see citing works
Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect
Sun, L., Suo, C., Li, S., Zhang, H., & Gao, P. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.005 · Cited by 366 · see citing works
The metabolic landscape of RAS-driven cancers from biology to therapy
Mukhopadhyay, S., Vander Heiden, M. G., & McCormick, F. (2021) · Nature Cancer · doi:10.1038/s43018-021-00184-x · Cited by 315 · see citing works
Role of lysosomes in physiological activities, diseases, and therapy
Zhang, Z., Yue, P., Lu, T., Wang, Y., Wei, Y., & Wei, X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01087-1 · Cited by 364 · see citing works
G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms
Bates, P. J., Reyes‐Reyes, E. M., Malik, M. T., Murphy, E. M., O’Toole, M. G., & Trent, J. O. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.12.015 · Cited by 348 · see citing works
Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors
Davidson, S. M., Jonas, O., Keibler, M. A., Hou, H. W., Luengo, A., Mayers, J. R., Wyckoff, J., Del Rosario, A. M., Whitman, M., Chin, C. R., et al. (2017) · Nature Medicine · doi:10.1038/nm.4256 · Cited by 331 · see citing works
Self-citationAspartate is an endogenous metabolic limitation for tumour growth
Sullivan, L. B., Luengo, A., Danai, L. V., Bush, L. N., Diehl, F. F., Hosios, A. M., Lau, A. N., Elmiligy, S., Malstrom, S. E., Lewis, C. A., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0125-0 · Cited by 339 · see citing works
Mechanoresponsive metabolism in cancer cell migration and metastasis
Zanotelli, M. R., Zhang, J., & Reinhart‐King, C. A. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.04.002 · Cited by 342 · see citing works
Binenbaum, Y., Fridman, E., Yaari, Z. A., Milman, N., Schroeder, A., David, G. B., Shlomi, T., & Gil, Z. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0124 · Cited by 339 · see citing works
Metabolic Codependencies in the Tumor Microenvironment
Dey, P., Kimmelman, A. C., & DePinho, R. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1211 · Cited by 342 · see citing works
A Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression
Auciello, F. R., Bulusu, V., Oon, C., Tait-Mulder, J., Berry, M., Bhattacharyya, S., Tumanov, S., Allen-Petersen, B. L., Link, J., Kendsersky, N. D., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1212 · Cited by 332 · see citing works
Self-citationCompensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism
Biancur, D. E., Paulo, J. A., Małachowska, B., Quiles Del Rey, M., Sousa, C. M., Wang, X., Sohn, A. S. W., Chu, G. C., Gygi, S. P., Harper, J. W., et al. (2017) · Nature Communications · doi:10.1038/ncomms15965 · Cited by 315 · see citing works
- Authors
- Commisso, C., Davidson, S. M., Soydaner-Azeloglu, R. G., Parker, S. J., Kamphorst, J. J., Hackett, S., Grabocka, E., Nofal, M., Drebin, J. A., Thompson, C. B., Rabinowitz, J. D., Metallo, C. M., Vander Heiden, M. G., & Bar-Sagi, D.
- Affiliations
- New York University (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of California San Diego (US)
- Princeton University (US)
- Hospital of the University of Pennsylvania (US)
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Nature
- Published
- 2013-05-12
- Volume
- 497
- Issue
- 7451
- Pages
- 633-637
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3810415
- OpenAlex
- W2129917557
- Cited by
- 1,683
- References
- 31
- Citations by year
- 2026: 120 · 2025: 130 · 2024: 130 · 2023: 136 · 2022: 162 · 2021: 186 · 2020: 166 · 2019: 135 · 2018: 129 · 2017: 113 · 2016: 119 · 2015: 79 · 2014: 56 · 2013: 20
- FWCI
- 52.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Cancer Institute (R01CA055360, P01CA104838, R01CA105463, P30CA014051, P01CA117969, P30CA016087, R01CA163591)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- macropinocytosis, oncogenic Ras, amino acid supply, glutamine addiction, cancer metabolism, macropinosomes, protein degradation, pancreatic tumours, nutrient uptake, cancer therapy
- MeSH terms
- Amino Acids, Animals, Biological Transport, Carbon, Cell Line, Transformed, Cell Transformation, Neoplastic, Disease Models, Animal, Female, Glutamine, Mice, Nude, Pancreatic Neoplasms, Pinocytosis, Oncogene Protein p21(ras), NIH 3T3 Cells, Cell Line, Tumor, Cell Proliferation, Mice, Proteolysis
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
