Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis
Open accessAbstract
Autophagy is a catabolic pathway used by cells to support metabolism in response to starvation and to clear damaged proteins and organelles in response to stress. We report here that expression of a H-ras V12 or K-ras V12 oncogene up-regulates basal autophagy, which is required for tumor cell survival in starvation and in tumorigenesis. In Ras-expressing cells, defective autophagosome formation or cargo delivery causes accumulation of abnormal mitochondria and reduced oxygen consumption. Autophagy defects also lead to tricarboxylic acid (TCA) cycle metabolite and energy depletion in starvation. As mitochondria sustain viability of Ras-expressing cells in starvation, autophagy is required to maintain the pool of functional mitochondria necessary to support growth of Ras-driven tumors. Human cancer cell lines bearing activating mutations in Ras commonly have high levels of basal autophagy, and, in a subset of these, down-regulating the expression of essential autophagy proteins impaired cell growth. As cancers with Ras mutations have a poor prognosis, this “autophagy addiction” suggests that targeting autophagy and mitochondrial metabolism are valuable new approaches to treat these aggressive cancers.
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?
RAS-driven cancers depend on autophagy for survival.
“RAS-driven cancers rely on autophagy for survival163, and this complex cellular process also seems to have immunomodulatory effects that promote tumour immune evasion.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [163]
In human cancer cell lines or tumors bearing KRAS mutations, high levels of basal autophagy were observed, making inhibition of autophagy therapeutically actionable in KRAS-driven tumors.
“in human cancer cell lines or tumors bearing KRAS mutations, high levels of basal autophagy were observed, making inhibition of autophagy therapeutically actionable in KRAS-driven tumors (64, 65).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [64]
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
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
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472 · see citing works
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865 · see citing works
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835 · see citing works
Impairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124 · see citing works
Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis
Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D., Chen, G., Mukherjee, C., Shi, Y., Gélinas, C., Fan, Y., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.06.001 · Cited by 2,013 · see citing works
Self-citationRabinowitz, J. D., & White, E. (2010) · Science · doi:10.1126/science.1193497 · Cited by 1,982 · see citing works
Self-citationMathew, R., Karantza-Wadsworth, V., & White, E. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2254 · Cited by 1,798 · see citing works
Self-citationMitochondrial 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
Autophagy Suppresses Tumorigenesis through Elimination of p62
Mathew, R., Karp, C. M., Beaudoin, B., Vuong, N., Chen, G., Chen, H.-Y., Bray, K., Reddy, A., Bhanot, G. V., Gélinas, C., et al. (2009) · Cell · doi:10.1016/j.cell.2009.03.048 · Cited by 1,723 · see citing works
Self-citationPancreatic cancers require autophagy for tumor growth
Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J. M., Dell'Antonio, G., et al. (2011) · Genes & Development · doi:10.1101/gad.2016111 · Cited by 1,498 · see citing works
Cancer's Molecular Sweet Tooth and the Warburg Effect
Kim, J., & Dang, C. V. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1501 · Cited by 1,217 · see citing works
The Double-Edged Sword of Autophagy Modulation in Cancer
White, E., & DiPaola, R. S. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5023 · Cited by 1,137 · see citing works
Self-citationAutophagy suppresses tumor progression by limiting chromosomal instabilityPreprint
Mathew, R., Kongara, S., Beaudoin, B., Karp, C. M., Bray, K., Degenhardt, K., Chen, G., Jin, S., & White, E. (2007) · Genes & Development · doi:10.1101/gad.1545107 · Cited by 938 · see citing works
Self-citationWu, M., Neilson, A., Swift, A. L., Moran, R., Tamagnine, J., Parslow, D., Armistead, S., Lemire, K., Orrell, J., Teich, J., et al. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00247.2006 · Cited by 922 · see citing works
Mitochondrial tumour suppressors: a genetic and biochemical update
Gottlieb, E., & Tomlinson, I. P. M. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1737 · Cited by 617 · see citing works
The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis
Duran, A., Linares, J. F., Galvez, A. S., Wikenheiser, K., Flores, J. M., Diaz-Meco, M. T., & Moscat, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.02.001 · Cited by 541 · see citing works
Dynamics of the Cellular Metabolome during Human Cytomegalovirus Infection
Munger, J. C., Bajad, S. U., Coller, H. A., Shenk, T. E., & Rabinowitz, J. D. (2006) · PLoS Pathogens · doi:10.1371/journal.ppat.0020132 · Cited by 417 · see citing works
Self-citationGenome-scale loss-of-function screening with a lentiviral RNAi library
Root, D. E., Hacohen, N., Hahn, W. C., Lander, E. S., & Sabatini, D. M. (2006) · Nature Methods · doi:10.1038/nmeth924 · Cited by 358 · see citing works
Role of autophagy in suppression of inflammation and cancer
White, E., Karp, C. M., Strohecker, A. M., Guo, Y., & Mathew, R. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.12.008 · Cited by 330 · see citing works
Self-citationDranka, B. P., Hill, B. G., & Darley-Usmar, V. M. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.01.015 · Cited by 329 · see citing works
Wu, J., Quijano, C., Chen, E., Liu, H., Cao, L., Fergusson, M. M., Rovira, I. I., Gutkind, S., Daniels, M. P., Komatsu, M., et al. (2009) · Aging · doi:10.18632/aging.100038 · Cited by 305 · see citing works
Hypoxia and defective apoptosis drive genomic instability and tumorigenesisPreprint
Nelson, D. A., Tan, T.-T., Rabson, A. B., Anderson, D., Degenhardt, K., & White, E. (2004) · Genes & Development · doi:10.1101/gad.1204904 · Cited by 281 · see citing works
Self-citationChoi, S. W., Gerencser, A. A., & Nicholls, D. G. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06055.x · Cited by 204 · see citing works
Bax and Bak Independently Promote Cytochrome cRelease from Mitochondria
Degenhardt, K., Sundararajan, R., Lindsten, T., Thompson, C. B., & White, E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109939200 · Cited by 195 · see citing works
Self-citationBAX and BAK mediate p53-independent suppression of tumorigenesis
Degenhardt, K., Chen, G., Lindsten, T., & White, E. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00126-5 · Cited by 140 · see citing works
Self-citationMitochondria get a Parkin' ticket
Wild, P. S., & Đikić, I. (2010) · Nature Cell Biology · doi:10.1038/ncb0210-104 · Cited by 60 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233 · 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
Levy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526 · see citing works
Wallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404 · see citing works
Self-consumption: the interplay of autophagy and apoptosis
Mariño, G., Niso-Santano, M., Baehrecke, E. H., & Kroemer, G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3735 · Cited by 2,172 · 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
RAS oncogenes: weaving a tumorigenic web
Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3106 · Cited by 1,789 · see citing works
NRF2 and the Hallmarks of Cancer
Rojo de la Vega, M., Chapman, E., & Zhang, D. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.022 · Cited by 1,672 · see citing works
Vyas, S., Zaganjor, E., & Haigis, M. C. (2016) · Cell · doi:10.1016/j.cell.2016.07.002 · Cited by 1,735 · see citing works
Pancreatic cancers require autophagy for tumor growth
Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J. M., Dell'Antonio, G., et al. (2011) · Genes & Development · doi:10.1101/gad.2016111 · Cited by 1,498 · see citing works
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438 · see citing works
The role for autophagy in cancer
White, E. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73941 · Cited by 1,332 · see citing works
Self-citationOncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function
Viale, A., Pettazzoni, P., Lyssiotis, C. A., Ying, H., Sánchez, N., Marchesini, M., Carugo, A., Green, T., Seth, S., Giuliani, V., et al. (2014) · Nature · doi:10.1038/nature13611 · Cited by 1,259 · see citing works
KRAS Mutation: From Undruggable to Druggable in Cancer
Huang, L., Guo, Z., Wang, F., & Fu, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00780-4 · Cited by 1,127 · see citing works
P53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080 · see citing works
The Roles of Autophagy in Cancer
Yun, C. W., & Lee, S. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113466 · Cited by 965 · see citing works
Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β
Dupont, N., Jiang, S., Pilli, M., Ornatowski, W., Bhattacharya, D., & Deretic, V. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.398 · Cited by 967 · 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-citationMetabolic control of autophagy
Galluzzi, L., Pietrocola, F., Levine, B., & Kroemer, G. (2014) · Cell · doi:10.1016/j.cell.2014.11.006 · Cited by 855 · 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
Self-citationAutophagy-dependent cell death
Denton, D., & Kumar, S. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0252-y · Cited by 777 · 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
Kamphorst, J. J., Cross, J. R., Fan, J., de Stanchina, E., Mathew, R., White, E. P., Thompson, C. B., & Rabinowitz, J. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307237110 · Cited by 726 · see citing works
Self-citationp53 status determines the role of autophagy in pancreatic tumour development
Rosenfeldt, M. T., O’Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., et al. (2013) · Nature · doi:10.1038/nature12865 · Cited by 713 · see citing works
Guo, J. Y., Karsli-Uzunbas, G., Mathew, R., Aisner, S. C., Kamphorst, J. J., Strohecker, A. M., Chen, G., Price, S., Lu, W., Teng, X., et al. (2013) · Genes & Development · doi:10.1101/gad.219642.113 · Cited by 589 · see citing works
Self-citationAutophagy is required for glucose homeostasis and lung tumor maintenance
Karsli-Uzunbas, G., Guo, J. Y., Price, S., Teng, X., Laddha, S. V., Khor, S., Kalaany, N. Y., Jacks, T., Chan, C. S., Rabinowitz, J. D., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0363 · Cited by 560 · see citing works
Self-citationThe current state of the art and future trends in RAS-targeted cancer therapies
Punekar, S. R., Velcheti, V., Neel, B. G., & Wong, K.-K. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00671-9 · Cited by 549 · see citing works
Genetics 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
Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy
Poillet-Perez, L., Despouy, G., Delage-Mourroux, R., & Boyer-Guittaut, M. (2015) · Redox Biology · doi:10.1016/j.redox.2014.12.003 · Cited by 503 · see citing works
Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations
Yang, A., Rajeshkumar, N. V., Wang, X., Yabuuchi, S., Alexander, B. M., Chu, G. C., Von Hoff, D. D., Maitra, A., & Kimmelman, A. C. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0362 · Cited by 486 · see citing works
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453 · see citing works
Inside and out: the activities of senescence in cancer
Pérez-Mancera, P. A., Young, A. R. J., & Narita, M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3773 · Cited by 462 · see citing works
Strohecker, A. M., Guo, J. Y., Karsli-Uzunbas, G., Price, S. M., Chen, G. J., Mathew, R., McMahon, M., & White, E. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0397 · Cited by 435 · see citing works
Self-citationEndoplasmic Reticulum Stress Signaling in Cancer Cells
Oakes, S. A. (2020) · The American Journal of Pathology · doi:10.1016/j.ajpath.2020.01.010 · Cited by 397 · 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
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
An essential role for functional lysosomes in ferroptosis of cancer cells
Torii, S., Shintoku, R., Kubota, C., Yaegashi, M., Torii, R., Sasaki, M., Suzuki, T., Mori, M., Yoshimoto, Y., Takeuchi, T., et al. (2016) · Biochemical Journal · doi:10.1042/bj20150658 · Cited by 349 · see citing works
Pasquier, B. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2104-y · Cited by 329 · see citing works
Lazova, R., Camp, R. L., Klump, V., Siddiqui, S. F., Amaravadi, R. K., & Pawelek, J. M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1282 · Cited by 305 · see citing works
The AMPK Inhibitor Compound C Is a Potent AMPK-Independent Antiglioma Agent
Liu, X., Chhipa, R. R., Nakano, I., & Dasgupta, B. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0579 · Cited by 288 · see citing works
Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A
Wong, P.-M., Feng, Y., Wang, J., Shi, R., & Jiang, X. (2015) · Nature Communications · doi:10.1038/ncomms9048 · Cited by 239 · see citing works
Gump, J. M., Staskiewicz, L., Morgan, M. J., Bamberg, A., Riches, D. W. H., & Thorburn, A. (2014) · Nature Cell Biology · doi:10.1038/ncb2886 · Cited by 230 · see citing works
Vazquez, A., Kamphorst, J. J., Markert, E. K., Schug, Z. T., Tardito, S., & Gottlieb, E. (2016) · Journal of Cell Science · doi:10.1242/jcs.181016 · Cited by 225 · see citing works
Self-citationThe Mechanism and Physiological Function of Macroautophagy
Klionsky, D. J., & Codogno, P. (2013) · Journal of Innate Immunity · doi:10.1159/000351979 · Cited by 221 · see citing works
Mechanisms of Selective Autophagy in Normal Physiology and Cancer
Mancias, J. D., & Kimmelman, A. C. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.027 · Cited by 196 · see citing works
Oncogenic KRAS induces NIX-mediated mitophagy to promote pancreatic cancer
Humpton, T. J., Alagesan, B., DeNicola, G. M., Lu, D., Yordanov, G. N., Leonhardt, C. S., Yao, M. A., Alagesan, P., Zaatari, M. N., Park, Y., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1409 · Cited by 198 · see citing works
The Autophagy Lysosomal Pathway and Neurodegeneration
Finkbeiner, S. (2020) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033993 · Cited by 196 · see citing works
Bott, A. J., Shen, J., Tonelli, C., Zhan, L., Sivaram, N., Jiang, Y.-P., Yu, X., Bhatt, V., Chiles, E., Zhong, H., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.056 · Cited by 185 · see citing works
Self-citationAutophagy Is a Protective Mechanism for Human Melanoma Cells under Acidic Stress
Marino, M. L., Pellegrini, P., Di Lernia, G., Djavaheri-Mergny, M., Brnjic, S., Zhang, X., Hägg, M., Linder, S., Fais, S., Codogno, P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.339127 · Cited by 184 · see citing works
RAS: Striking at the Core of the Oncogenic Circuitry
Gimple, R. C., & Wang, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00965 · Cited by 174 · see citing works
Kang, R., Loux, T., Tang, D., Schapiro, N. E., Vernon, P., Livesey, K. M., Krasinskas, A., Lotze, M. T., & Zeh, H. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113865109 · Cited by 163 · see citing works
Coordinate Autophagy and mTOR Pathway Inhibition Enhances Cell Death in Melanoma
Xie, X., White, E. P., & Mehnert, J. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055096 · Cited by 150 · see citing works
Self-citationPIKfyve Regulates Vacuole Maturation and Nutrient Recovery following Engulfment
Krishna, S., Palm, W., Lee, Y., Yang, W., Bandyopadhyay, U., Xu, H., Florey, O., Thompson, C. B., & Overholtzer, M. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.08.001 · Cited by 140 · see citing works
Differential effector engagement by oncogenic KRAS
Yuan, T. L., Amzallag, A., Bagni, R., Yi, M., Afghani, S., Burgan, W., Fer, N., Strathern, L. A., Powell, K., Smith, B., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.051 · Cited by 150 · see citing works
New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness
Yang, H., Liang, S.-Q., Schmid, R. A., & Peng, R.-W. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00953 · Cited by 129 · see citing works
MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival
Lee, C.-S., Lee, L. C., Yuan, T. L., Chakka, S., Fellmann, C., Lowe, S. W., Caplen, N. J., McCormick, F., & Luo, J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1817494116 · Cited by 126 · see citing works
Altered energy metabolism in cancer: A unique opportunity for therapeutic intervention
Zhang, Y., & Yang, J.-M. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.22958 · Cited by 132 · see citing works
Functional genomics in vivo reveal metabolic dependencies of pancreatic cancer cells
Zhu, X. G., Chudnovskiy, A., Baudrier, L., Prizer, B., Liu, Y., Ostendorf, B. N., Yamaguchi, N., Arab, A., Tavora, B., Timson, R., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.017 · Cited by 130 · see citing works
Mealer, R. G., Murray, A. J., Shahani, N., Subramaniam, S., & Snyder, S. H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.536912 · Cited by 124 · see citing works
Autophagic activity dictates the cellular response to oncogenic RAS
Wang, Y., Wang, X. D., Lapi, E., Sullivan, A., Jia, W., He, Y.-W., Ratnayaka, I., Zhong, S., Goldin, R. D., Goemans, C. G., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120193109 · Cited by 117 · see citing works
Synthetic Lethal Vulnerabilities in <i>KRAS</i>-Mutant Cancers
Aguirre, A. J., & Hahn, W. C. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031518 · Cited by 90 · see citing works
Targeting LKB1 in Cancer – Exposing and Exploiting Vulnerabilities
Momcilovic, M., & Shackelford, D. B. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.261 · Cited by 97 · see citing works
Relationship between growth arrest and autophagy in midgut programmed cell death in Drosophila
Denton, D., Chang, T.-K., Nicolson, S., Shravage, B., Simin, R., Baehrecke, E. H., & Kumar, S. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.43 · Cited by 81 · see citing works
Autophagy role(s) in response to oncogenes and DNA replication stress
Vanzo, R., Bartkova, J., Merchut-Maya, J. M., Hall, A., Bouchal, J., Dyrskjøt, L., Frankel, L. B., Gorgoulis, V., Maya-Mendoza, A., Jäättelä, M., et al. (2020) · Cell Death & Differentiation · doi:10.1038/s41418-019-0403-9 · Cited by 79 · see citing works
Schonewolf, C. A., Mehta, M., Schiff, D., Wu, H., Haffty, B. G., Karantza, V., & Jabbour, S. K. (2014) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v6.i3.74 · Cited by 71 · see citing works
Self-citationWang, C., Chen, S., Yeo, S., Karsli-Uzunbas, G., White, E., Mizushima, N., Virgin, H. W., & Guan, J.-L. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201507023 · Cited by 69 · see citing works
Self-citationThe Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death
Velentzas, P. D., Zhang, L., Das, G., Chang, T.-K., Nelson, C., Kobertz, W. R., & Baehrecke, E. H. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.09.015 · Cited by 31 · see citing works
Sastre-Serra, J., Nadal-Serrano, M., Pons, D. G., Roca, P., & Oliver, J. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.04.007 · Cited by 34 · see citing works
Targeting autophagy as a therapeutic strategy against pancreatic cancer
Yamamoto, K., Iwadate, D., Kato, H., Nakai, Y., Tateishi, K., & Fujishiro, M. (2022) · Journal of Gastroenterology · doi:10.1007/s00535-022-01889-1 · Cited by 29 · see citing works
Hanada, K., Kawada, K., Nishikawa, G., Toda, K., Maekawa, H., Nishikawa, Y., Masui, H., Hirata, W., Okamoto, M., Kiyasu, Y., et al. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.09.023 · Cited by 27 · see citing works
Oncogene Overdose: Too Much of a Bad Thing for Oncogene-Addicted Cancer Cells
Amin, A. D., Rajan, S. S., Groysman, M. J., Pongtornpipat, P., & schatz, J. H. (2015) · Biomarkers in Cancer · doi:10.4137/bic.s29326 · Cited by 25 · see citing works
- Authors
- Guo, J. Y., Chen, H.-Y., Mathew, R., Fan, J., Strohecker, A. M., Karsli-Uzunbas, G., Kamphorst, J. J., Chen, G., Lemons, J. M. S., Karantza, V., Coller, H. A., DiPaola, R. S., Gelinas, C., Rabinowitz, J. D., & White, E.
- Affiliations
- Rutgers Cancer Institute (US)
- Rutgers, The State University of New Jersey (US)
- Princeton University (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-02-11
- Volume
- 25
- Issue
- 5
- Pages
- 460-470
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3049287
- OpenAlex
- W2101228747
- Cited by
- 1,323
- References
- 33
- Citations by year
- 2026: 27 · 2025: 56 · 2024: 58 · 2023: 70 · 2022: 88 · 2021: 120 · 2020: 91 · 2019: 95 · 2018: 105 · 2017: 97 · 2016: 95 · 2015: 86 · 2014: 92 · 2013: 106 · 2012: 76
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Rutgers Cancer Institute of New Jersey
- National Institutes of Health (R37 CA53370)
- National Cancer Institute (R37CA053370, R37-CA53370, R00CA133181, RC1CA147961, R01CA130893, P30CA072720)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- autophagy, oncogenic Ras, H-Ras V12, carcinogenesis, mitochondrial metabolism, oxidative metabolism, starvation, autophagosome formation, mitochondrial dysfunction, TCA cycle metabolites, oxygen consumption, cancer therapy targets
- MeSH terms
- Animals, Autophagy, Cell Line, Cell Survival, Energy Metabolism, Humans, Mitochondria, Oxidation-Reduction, Genes, ras, Starvation, Gene Expression Regulation, Neoplastic, HCT116 Cells, Cell Line, Tumor, Cell Proliferation, Mice
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
