Induction of Autophagy during Extracellular Matrix Detachment Promotes Cell Survival
Open accessAbstract
Autophagy has been proposed to promote cell death during lumen formation in three-dimensional mammary epithelial acini because numerous autophagic vacuoles are observed in the dying central cells during morphogenesis. Because these central cells die due to extracellular matrix (ECM) deprivation (anoikis), we have directly interrogated how matrix detachment regulates autophagy. Detachment induces autophagy in both nontumorigenic epithelial lines and in primary epithelial cells. RNA interference-mediated depletion of autophagy regulators (ATGs) inhibits detachment-induced autophagy, enhances apoptosis, and reduces clonogenic recovery after anoikis. Remarkably, matrix-detached cells still exhibit autophagy when apoptosis is blocked by Bcl-2 overexpression, and ATG depletion reduces the clonogenic survival of Bcl-2-expressing cells after detachment. Finally, stable reduction of ATG5 or ATG7 in MCF-10A acini enhances luminal apoptosis during morphogenesis and fails to elicit long-term luminal filling, even when combined with apoptotic inhibition mediated by Bcl-2 overexpression. Thus, autophagy promotes epithelial cell survival during anoikis, including detached cells harboring antiapoptotic lesions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Anoikis has been reported in the formation of the lumen during the development of various secretory glands such as mammary and salivary glands.
“Anoikis, a form of apoptosis caused by inappropriate cell/ECM interactions, has been reported in the formation of the lumen during the development of various secretory glands such as mammary and salivary glands.[20,21]”
From Autophagy, not apoptosis, plays a role in lumen formation of eccrine gland organoids (2022) · cites this paper as [21]
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Dissemination and growth of cancer cells in metastatic sites
Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002) · Nature reviews. Cancer · doi:10.1038/nrc865 · Cited by 3,920 · see citing works
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · see citing works
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
Pattingre, S., Tassa, A., Qu, X., Garuti, R., Liang, X. H., Mizushima, N., Packer, M., Schneider, M. D., & Levine, B. (2005) · Cell · doi:10.1016/j.cell.2005.07.002 · Cited by 3,536 · see citing works
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347 · see citing works
Disruption of epithelial cell-matrix interactions induces apoptosis
Frisch, S., & Francis, H. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.4.619 · Cited by 3,272 · 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
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311 · see citing works
Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116 · 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
Debnath, J., Muthuswamy, S. K., & Brugge, J. S. (2003) · Methods · doi:10.1016/s1046-2023(03)00032-x · Cited by 2,001 · see citing works
Self-citationAutophagy Is Activated for Cell Survival after Endoplasmic ReticulumStress
Ogata, M., Hino, S.-I., Saito, A., Morikawa, K., Kondo, S., Kanemoto, S., Murakami, T., Taniguchi, M., Tanii, I., Yoshinaga, K., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01453-06 · Cited by 1,832 · see citing works
Autophagy in cell death: an innocent convict?
Levine, B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26390 · Cited by 1,671 · see citing works
Inhibition of Macroautophagy Triggers Apoptosis
Boya, P., González‐Polo, R. A., Casares, N., Perfettini, J., Dessen, P., Larochette, N., Métivier, D., Meley, D., Souquère, S., Yoshimori, T., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.3.1025-1040.2005 · Cited by 1,629 · see citing works
The extracellular matrix as a cell survival factor.
Meredith, J. E., Fazeli, B., & Schwartz, M. A. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.9.953 · Cited by 1,540 · see citing works
Growth factor regulation of autophagy and cell survival in the absence of apoptosis
Lum, J. J., Bauer, D. E., Kong, M., Harris, M. H., Li, C., Lindsten, T., & Thompson, C. B. (2005) · Cell · doi:10.1016/j.cell.2004.11.046 · Cited by 1,487 · see citing works
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358 · see citing works
A Unified Nomenclature for Yeast Autophagy-Related Genes
Klionsky, D. J., Cregg, J. M., Dunn, W. A., Emr, S. D., Sakai, Y., Sandoval, I. V., Sibirny, A. А., Subramani, S. E., Thumm, M., Marten Veenhuis, A., et al. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00296-x · Cited by 1,267 · see citing works
Regulation of an ATG7 - beclin 1 Program of Autophagic Cell Death by Caspase-8
Yu, L., Alva, A. S., Su, H. C., Dutt, P., Freundt, E. C., Welsh, S. J., Baehrecke, E. H., & Lenardo, M. J. (2004) · Science · doi:10.1126/science.1096645 · Cited by 1,220 · see citing works
Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy
Tanida, I., Minematsu-Ikeguchi, N., Ueno, T., & Kominami, E. (2005) · Autophagy · doi:10.4161/auto.1.2.1697 · Cited by 1,108 · cited 2× · see citing works
“In this study, the observed reductions in autophagy were based exclusively on measurements of GFP-LC3 puncta; thus, it remains unknown whether the reductions in punctate GFP-LC3 observed upon integrin blockade are actually due to decreased autophagosome formation versus increased LC3-II turnover in the lysosome (Tanid…”
BackgroundControl of Macroautophagy by Calcium, Calmodulin-Dependent Kinase Kinase-β, and Bcl-2
Høyer-Hansen, M., Bastholm, L., Szyniarowski, P., Campanella, M., Szabadkai, G., Farkas, T., Bianchi, K., Fehrenbacher, N., Elling, F., Rizzuto, R., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.12.009 · Cited by 1,072 · see citing works
Modelling glandular epithelial cancers in three-dimensional cultures
Debnath, J., & Brugge, J. S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1695 · Cited by 1,014 · 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
Kouroku, Y., Fujita, E., Tanida, I., Ueno, T., Isoai, A., Kumagai, H., Ogawa, S., Kaufman, R. J., Kominami, E., & Momoi, T. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401984 · Cited by 934 · see citing works
Liang, J., Shao, S. H., Xu, Z.-X., Hennessy, B. T., Ding, Z., Larrea, M. D., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1537 · Cited by 868 · see citing works
Sensing the environment: a historical perspective on integrin signal transduction
Miranti, C. K., & Brugge, J. S. (2002) · Nature Cell Biology · doi:10.1038/ncb0402-e83 · Cited by 851 · see citing works
Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesisPreprint
Karantza‐Wadsworth, V., Patel, S. A., Kravchuk, O., Chen, G., Mathew, R., Jin, S., & White, E. (2007) · Genes & Development · doi:10.1101/gad.1565707 · Cited by 841 · see citing works
Debnath, J., Mills, K. R., Collins, N. L., Reginato, M. J., Muthuswamy, S. K., & Brugge, J. S. (2002) · Cell · doi:10.1016/s0092-8674(02)01001-2 · Cited by 763 · see citing works
Self-citationRegulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway
Tallóczy, Z., Jiang, W., Virgin, H. W., Leib, D. A., Scheuner, D. L., Kaufman, R. J., Eskelinen, E., & Levine, B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012485299 · Cited by 741 · see citing works
Integrins in Mechanotransduction
Katsumi, A., Orr, A. W., Tzima, E., & Schwartz, M. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r300038200 · Cited by 724 · see citing works
Autophagic programmed cell death by selective catalase degradation
Yu, L., Wan, F., Dutta, S., Welsh, S., Liu, Z., Freundt, E. C., Baehrecke, E. H., & Lenardo, M. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511288103 · Cited by 668 · see citing works
Autophagy Gene-Dependent Clearance of Apoptotic Cells during Embryonic Development
Qu, X., Zou, Z., Sun, Q., Luby‐Phelps, K., Cheng, P., Hogan, R. N., Gilpin, C. J., & Levine, B. (2007) · Cell · doi:10.1016/j.cell.2006.12.044 · Cited by 655 · see citing works
Gilmore, A. P. (2005) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401723 · Cited by 597 · see citing works
Kuma, A., Matsui, M., & Mizushima, N. (2007) · Autophagy · doi:10.4161/auto.4012 · Cited by 555 · cited 1× · see citing works
“Because transient GFP-LC3 transfection can produce overexpression artifacts, we developed retroviral vectors (pBABE) encoding GFP-LC3, and we generated stable pools ectopically expressing these fusions (Kuma et al., 2007).”
BackgroundIntegrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis
Reginato, M. J., Mills, K. R., Paulus, J. K., Lynch, D. K., Sgroi, D. C., Debnath, J., Muthuswamy, S. K., & Brugge, J. S. (2003) · Nature Cell Biology · doi:10.1038/ncb1026 · Cited by 545 · see citing works
Self-citationInbal, B., Bialik, S., Sabanay, I., Shani, G., & Kimchi, A. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200109094 · Cited by 476 · see citing works
AMP-activated Protein Kinase and the Regulation of Autophagic Proteolysis
Meley, D., Bauvy, C., Houben-Weerts, J. H. P. M., Dubbelhuis, P. F., Helmond, M. T. J., Codogno, P., & Meijer, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605488200 · Cited by 461 · see citing works
Does Autophagy Contribute To Cell Death?
Debnath, J., Baehrecke, E. H., & Kroemer, G. (2005) · Autophagy · doi:10.4161/auto.1.2.1738 · Cited by 444 · see citing works
Self-citationAutophagy: a barrier or an adaptive response to cancer
Ogier‐Denis, É., & Codogno, P. (2003) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(03)00004-0 · Cited by 365 · see citing works
Steroid regulation of autophagic programmed cell death during development
Lee, C.-Y., & Baehrecke, E. H. (2001) · Development · doi:10.1242/dev.128.8.1443 · Cited by 336 · see citing works
Caspases function in autophagic programmed cell death inDrosophila
Martin, D. N., & Baehrecke, E. H. (2003) · Development · doi:10.1242/dev.00933 · Cited by 258 · see citing works
Mills, K. R., Reginato, M. J., Debnath, J., Queenan, B., & Brugge, J. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400443101 · Cited by 242 · see citing works
Self-citationMetabolic catastrophe as a means to cancer cell death
Jin, S., DiPaola, R. S., Mathew, R., & White, E. (2007) · Journal of Cell Science · doi:10.1242/jcs.03349 · Cited by 229 · see citing works
Rytömaa, M., Lehmann, K. E., & Downward, J. (2000) · Oncogene · doi:10.1038/sj.onc.1203805 · Cited by 132 · see citing works
Petrovski, G., Zahuczky, G., Katona, K., Vereb, G., Martinet, W., Nemes, Z., Bursch, W., & Fésüs, L. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402112 · Cited by 77 · see citing works
Edick, M. J., Tesfay, L., Lamb, L. E., Knudsen, B. S., & Miranti, C. K. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-04-0261 · Cited by 75 · see citing works
The ultrastructure of MCF‐10A acini
Underwood, J. M., Imbalzano, K. M., Weaver, V. M., Fischer, A. H., Imbalzano, A. N., & Nickerson, J. A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20639 · Cited by 73 · see citing works
Activation of NF-κB following detachment delays apoptosis in intestinal epithelial cells
Yan, S. R., Joseph, R. R., Rosen, K. V., Reginato, M. J., Jackson, A. M., Allaire, N., Brugge, J. S., Jobin, C., & Stadnyk, A. W. (2005) · Oncogene · doi:10.1038/sj.onc.1208810 · Cited by 55 · see citing works
Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells
Liu, Z., Li, H., Wu, X., Yoo, B. H., Yan, S. R., Stadnyk, A. W., Sasazuki, T., Shirasawa, S., LaCasse, E. C., Korneluk, R. G., et al. (2006) · Oncogene · doi:10.1038/sj.onc.1209753 · Cited by 54 · see citing works
Frisch, S. M. (2003) · Humana Press eBooks · doi:10.1385/1-59259-249-x:251 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Deconvoluting the context-dependent role for autophagy in cancer
White, E. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3262 · Cited by 1,698 · 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
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,653 · see citing works
“Once the metastatic cancer cells successfully establish distant colonies in their destination organs, autophagy begins to play a critical role and the autophagic flux is induced to respond various environmental stress including hypoxia, nutrient deprivation and detachment from the ECM [187, 240, 247, 248].”
BackgroundAutophagy and autophagy-related pathways in cancer
Debnath, J., Gammoh, N., & Ryan, K. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00585-z · Cited by 1,443 · 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
Life and death partners: apoptosis, autophagy and the cross-talk between them
Eisenberg‐Lerner, A., Bialik, S., Simon, H.-U., & Kimchi, A. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.33 · Cited by 1,183 · see citing works
Anoikis molecular pathways and its role in cancer progression
Paoli, P., Giannoni, E., & Chiarugi, P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.026 · Cited by 1,160 · see citing works
“In this context, autophagy may provide a temporary survival mechanism, which delay the onset of apoptosis, thus giving cells the chance to survive and reactivate once they reattach to the ECM [76,108].”
BackgroundApoptosis, autophagy, necroptosis, and cancer metastasis
Su, Z., Yang, Z., Xu, Y., Chen, Y., & Yu, Q. (2015) · Molecular Cancer · doi:10.1186/s12943-015-0321-5 · Cited by 1,039 · see citing works
“Another study showed that autophagy was induced by either matrix detachment or β1 integrin inhibition [100].”
BackgroundAntioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment
Schafer, Z. T., Grassian, A. R., Song, L., Jiang, Z., Gerhart-Hines, Z., Irie, H. Y., Gao, S., Puigserver, P., & Brugge, J. S. (2009) · Nature · doi:10.1038/nature08268 · Cited by 1,031 · see citing works
Self-citationThe 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
“Another study indicates that autophagy induces ECM detachment and the inhibition of β1 integrin [109].”
BackgroundROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway
Zhao, Y., Hu, X., Liu, Y., Dong, S., Wen, Z., He, W., Zhang, S., Huang, Q., & Shi, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0648-1 · Cited by 735 · see citing works
“Under ECM-detached condition, AMPK promotes survival by autophagy induction and global inhibition of protein synthesis, mitigating the ATP reduction [99, 100].”
Anoikis: an emerging hallmark in health and diseases
Taddei, M., Giannoni, E., Fiaschi, T., & Chiarugi, P. (2011) · The Journal of Pathology · doi:10.1002/path.3000 · Cited by 719 · see citing works
He, C., & Levine, B. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.01.001 · Cited by 659 · 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
“induces autophagy which in return provides resistance to anoikis [57,86,87] which is necessary for the metastasis of hepatocellular carcinoma (HCC) and mammary epithelial cells (MEC) [88,89].”
BackgroundAutophagy 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
“Intriguingly, some preliminary work has also suggested that specific components of the ECM, including collagen VI and laminin α 2 (80), can modulate intracellular autophagy through as-yet unknown mechanisms.”
InfluentialAutophagy facilitates glycolysis during Ras-mediated oncogenic transformation
Lock, R., Roy, S., Kenific, C. M., Su, J. S., Salas, E., Ronen, S. M., & Debnath, J. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-06-0500 · Cited by 467 · see citing works
“For example, increased autophagy is observed in cells centrally located within solid tumors that lack access to nutrients and oxygen; genetic inhibition of autophagy results in the increased death of these stressed tumor cells ( Degenhardt et al. , 2006 ).”
BackgroundMethodInfluentialSelf-citationAutophagy: for better or for worse
Wirawan, E., Berghe, T. V., Lippens, S., Agostinis, P., & Vandenabeele, P. (2011) · Cell Research · doi:10.1038/cr.2011.152 · Cited by 468 · see citing works
Anoikis Resistance: An Essential Prerequisite for Tumor Metastasis
Kim, Y.-N., Koo, K. H., Sung, J. Y., Yun, U.-J., & Kim, H. (2012) · International Journal of Cell Biology · doi:10.1155/2012/306879 · Cited by 461 · see citing works
“Silencing of autophagy regulators inhibits detachment-induced autophagy and enhances apoptosis, indicating that autophagy promotes epithelial cell survival during anoikis [91].”
BackgroundInfluentialMAPK/JNK signalling: a potential autophagy regulation pathway
Zhou, Y.-Y., Li, Y., Jiang, W.-Q., & Zhou, L.-F. (2015) · Bioscience Reports · doi:10.1042/bsr20140141 · Cited by 444 · see citing works
Control of autophagy by oncogenes and tumor suppressor genes
Maiuri, M. C., Tasdemir, E., Criollo, A., Morselli, E., Vicencio, J. M., Carnuccio, R., & Kroemer, G. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.131 · Cited by 433 · see citing works
Overcoming anoikis – pathways to anchorage-independent growth in cancer
Guadamillas, M. C., Cerezo, A., & del Pozo, M. Á. (2011) · Journal of Cell Science · doi:10.1242/jcs.072165 · Cited by 425 · see citing works
“This TRAIL-induced autophagy appears to counteract mammary gland lumen formation, contrary to the observations made by Mills and colleagues (Herrero-Martin et al., 2009) because the inhibition of this process enhanced luminal apoptosis (Fung et al., 2008).”
BackgroundResultTumor Vessel Normalization by Chloroquine Independent of Autophagy
Maes, H., Kuchnio, A., Peric, A., Moens, S., Nys, K., Bock, K. D., Quaegebeur, A., Schoors, S., Γεωργιάδου, Μ., Wouters, J., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.06.025 · Cited by 411 · see citing works
“Regarding the mechanisms of metastasis, ATG5-silenced cancer cells also failed to colonize the lungs after intravenous injection, most likely because of their increased vulnerability to anoikis (Fung et al., 2008).”
BackgroundCrosstalk between mechanotransduction and metabolism
Romani, P., Valcárcel-Jiménez, L., Frezza, C., & Dupont, S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00306-w · Cited by 409 · see citing works
TAK1 activates AMPK‐dependent cytoprotective autophagy in TRAIL‐treated epithelial cells
Herrero‐Martín, G., Høyer‐Hansen, M., García‐García, C., Fumarola, C., Farkas, T., López‐Rivas, A., & Jäättelä, M. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.8 · Cited by 400 · see citing works
“Accordingly, autophagy inhibition by depletion of Atg5 or Atg7 has recently been shown to enhance luminal apoptosis in an MCF10A breast morphogen- esis model (Fung et al, 2008).”
BackgroundMaycotte, P., & Thorburn, A. M. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.14627 · Cited by 394 · see citing works
Autophagy as a molecular target for cancer treatment
Kocatürk, N. M., Akkoç, Y., Kığ, C., Bayraktar, O., Gözüaçık, D., & Kutlu, Ö. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.04.011 · Cited by 388 · see citing works
Anti- and pro-tumor functions of autophagy
Morselli, E., Galluzzi, L., Kepp, O., Vicencio, J. M., Criollo, A., Maiuri, M. C., & Kroemer, G. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.01.006 · Cited by 377 · see citing works
“, anoikis) [95,96]; estrogen receptor antagonism with tamoxifen [97]; androgendeprivation [98]; radiation therapy [99]; DNA alkylation damage with cyclophosphamide [76] or temozolomide [100]; inhibition of TKRs with imatinib [101]; inhibition of cyclooxygenases with sulindac sulfide [102]; as well as N-(4-hydroxypheny…”
MethodCopper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma
Tsang, T., Posimo, J. M., Gudiel, A. A., Cicchini, M., Feldser, D. M., & Brady, D. C. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0481-4 · Cited by 373 · see citing works
Gong, C., Bauvy, C., Tonelli, G., Yue, W., Deloménie, C., Nicolas, V., Zhu, Y., Domergue, V., Marin‐Esteban, V., Tharinger, H., et al. (2012) · Oncogene · doi:10.1038/onc.2012.252 · Cited by 369 · see citing works
Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression
Buchheit, C. L., Weigel, K. J., & Schafer, Z. T. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3789 · Cited by 367 · see citing works
Autophagy and apoptosis in liver injury
Wang, K. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1038685 · Cited by 363 · see citing works
“The loss of matrix attachment induces apoptotic cell death.(65,66) Collectively, autophagy antagonizes apoptosis and promotes cell survival via a series of response to damaged organelles, ER stress, DNA stability, or loss of nutrient and growth factor signaling pathways.”
BackgroundPLIC proteins or ubiquilins regulate autophagy‐dependent cell survival during nutrient starvation
N'Diaye, E., Kajihara, K. K., Hsieh, I., Morisaki, H., Debnath, J., & Brown, E. J. (2009) · The EMBO Reports · doi:10.1038/embor.2008.238 · Cited by 323 · see citing works
“When stably transfected with control or ATG7 short hairpin RNA (Fung et al, 2008), cells were maintained under 2 mg/ml of puromycin selection.”
BackgroundMethodInfluentialSelf-citationContact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis
Tanasa, M. P., Renna, M., Park, S. J., Menzies, F. M., Ricketts, T., Füllgrabe, J., Ashkenazi, A., Frake, R. A., Carnicer‐Lombarte, A., Bento, C. F., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05388-x · Cited by 318 · see citing works
Therapeutic targets in cancer cell metabolism and autophagy
Cheong, H., Lü, C., Lindsten, T., & Thompson, C. B. (2012) · Nature Biotechnology · doi:10.1038/nbt.2285 · Cited by 316 · see citing works
Sharifi, M. N., Mowers, E. E., Drake, L. E., Collier, C., Chen, H., Zamora, M. A., Mui, S. R., & Macleod, K. F. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.065 · Cited by 315 · see citing works
“The known functions of autophagy in promoting cell survival during extracellular matrix (ECM) detachment, growth factor withdrawal, and nutrient deprivation (Fung et al., 2008; Kuma et al., 2004) are believed to promote progression following escape from the primary tumor.”
Autophagy and metastasis: another double-edged sword
Kenific, C. M., Thorburn, A. M., & Debnath, J. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.10.008 · Cited by 312 · see citing works
“Specifically, suppression of b1 integrin signaling, a known inducer of autophagy, promotes dormancy in the MMTV–PyMT model of breast cancer [22 ,29].”
Self-citationThe Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity
Chavez-Dominguez, R., Perez-Medina, M., López-González, J. S., Galicia-Velasco, M., & Aguilar‐Cázares, D. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.578418 · Cited by 309 · see citing works
“(127), showed in a 3D oncogenesis model of breast epithelial cultures, that cell shedding from ECM induces autophagy and tumor cell survival.”
BackgroundATG12–ATG3 interacts with Alix to promote basal autophagic flux and late endosome function
Murrow, L. M., Malhotra, R., & Debnath, J. (2015) · Nature Cell Biology · doi:10.1038/ncb3112 · Cited by 301 · see citing works
Self-citationAutophagy as a therapeutic target in cancer
Chen, N., & Karantza, V. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.14622 · Cited by 303 · see citing works
The multiple roles of autophagy in cancer
Rosenfeldt, M. T., & Ryan, K. M. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr031 · Cited by 302 · see citing works
Peng, Y., Shi, Y., Ding, Z., Ke, A., Gu, C., Hui, B., Zhou, J., Qiu, S., Dai, Z., & Fan, J. (2013) · Autophagy · doi:10.4161/auto.26398 · Cited by 296 · see citing works
ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death
Radoshevich, L., Murrow, L., Chen, N., Fernandez, E., Roy, S., Fung, C., & Debnath, J. (2010) · Cell · doi:10.1016/j.cell.2010.07.018 · Cited by 290 · see citing works
“A peptide corresponding to the N terminus common to human, mouse, and rat MAP1LC3 was used to create a-LC3 rabbit polyclonal antibody (Fung et al., 2008).”
Self-citationAutophagy and mitophagy in cancer metabolic remodelling
Ferro, F., Servais, S., Besson, P., Roger, S., Dumas, J., & Brisson, L. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.029 · Cited by 285 · see citing works
“thus allowing cancer cell survival in vessels and during metastatic colonization [43, 44].”
BackgroundAutophagy-Dependent Production of Secreted Factors Facilitates Oncogenic RAS-Driven Invasion
Lock, R., Kenific, C. M., Leidal, A. M., Salas, E., & Debnath, J. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0841 · Cited by 280 · see citing works
“During normal MCF10A acinar morphogenesis, autophagy inhibition results in the enhanced apoptosis of cells occupying the luminal space (17).”
Self-citationAvivar‐Valderas, A., Salas, E., Bobrovnikova-Marjon, E. V., Diehl, J. A., Nagi, C. S., Debnath, J., & Aguirre‐Ghiso, J. A. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05164-11 · Cited by 280 · see citing works
“Because ECM detachment can induce autophagy (16) and PERK can activate autophagy (24, 27, 34), we first tested whether PERK activation in suspension was responsible for autophagy induction.”
BackgroundMethodInfluentialSelf-citationKoesters, R., Kaissling, B., LeHir, M., Picard, N., Theilig, F., Gebhardt, R., Glick, A. B., Hähnel, B., Hosser, H., Gröne, H., et al. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091012 · Cited by 271 · see citing works
Autophagy: shaping the tumor microenvironment and therapeutic response
Maes, H., Rubio, N., Garg, A. D., & Agostinis, P. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.04.005 · Cited by 266 · see citing works
Tsvetkov, A. S., Miller, J., Arrasate, M., Wong, J. S., Pleiss, M. A., & Finkbeiner, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004498107 · Cited by 266 · see citing works
“16982–16987 | PNAS | September 28, 2010 | vol. 107 | no. 39 www.pnas.org/cgi/doi/10.1073/pnas.1004498107 If 10-NCP increases LC3-II levels by promoting autophagy, it should induce formation of GFP-LC3-positive autophagosomes in GFP-LC3 transgenic neurons (15).”
BackgroundMethodInfluentialGalavotti, S., Bartesaghi, S., Faccenda, D., Shaked-Rabi, M., Sanzone, S., McEvoy, A. W., Dinsdale, D. D., Condorelli, F., Brandner, S., Campanella, M., et al. (2012) · Oncogene · doi:10.1038/onc.2012.111 · Cited by 266 · see citing works
Cellular and metabolic functions for autophagy in cancer cells
Kenific, C. M., & Debnath, J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.09.001 · Cited by 261 · see citing works
“Autophagy was first shown to promote the survival of non-transformed mammary epithelial cells during ECM detachment; subsequent studies revealed that detachment-induced autophagy is critical for adhesion-independent transformation [20, 44].”
BackgroundSelf-citationChaperone-Mediated Autophagy Is Required for Tumor Growth
Kon, M., Kiffin, R., Koga, H., Chapochnick, J., Macián, F., Varticovski, L., & Cuervo, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003182 · Cited by 260 · see citing works
Autophagy regulation and its role in cancer
Lorin, S., Hamaï, A., Mehrpour, M., & Codogno, P. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.06.007 · Cited by 247 · see citing works
The autophagic paradox in cancer therapy
Wu, W., Coffelt, S., Chi, H.-C., Wang, X., Lee, C. W., Chan, F., Yu, J., & Sung, J. J. (2012) · Oncogene · doi:10.1038/onc.2011.295 · Cited by 260 · see citing works
“In this regard, autophagy protects cancer cells against various forms of cellular insults, including endoplasmic reticulum stress, loss of contact with the extracellular matrix and toxicities of cancer therapy (Fung et al., 2008; Levine and Kroemer, 2008; Wu et al., 2010b).”
BackgroundMolecular Regulation of Lumen Morphogenesis
Datta, A., Bryant, D. M., & Mostov, K. E. (2011) · Current Biology · doi:10.1016/j.cub.2010.12.003 · Cited by 242 · see citing works
“Surprisingly, autophagy suppresses, rather than promotes, apoptosis [88], suggesting that our understanding of luminal clearance is incomplete.”
BackgroundJain, M. V., Paczulla, A., Klonisch, T. C., Dimgba, F. N., Rao, S. B., Roberg, K. B., Schweizer, F., Lengerke, C., Davoodpour, P., Palicharla, V. R., et al. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12001 · Cited by 241 · see citing works
“Autophagy integrates with oxidative stress responses to promote survival of cells during anoikis (detachment of cells from extracellular matrix) [95, 96].”
BackgroundDoes autophagy have a license to kill mammalian cells?
Scarlatti, F., Granata, R., Meijer, A., & Codogno, P. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2008.101 · Cited by 271 · see citing works
Bhutia, S. K., Mukhopadhyay, S., Sinha, N., Das, D. N., Panda, P. K., Patra, S. K., Maiti, T. K., Mandal, M., Dent, P., Wang, X., et al. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407173-5.00003-0 · Cited by 230 · see citing works
Chen, N., & Debnath, J. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.12.034 · Cited by 224 · see citing works
“Tumor cells must overcome anoikis in order to metastasize [22].”
BackgroundSelf-citationThe dual role of autophagy in cancer
Eskelinen, E. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.03.009 · Cited by 222 · see citing works
Autophagy and cancer – issues we need to digest
Liu, E. Y., & Ryan, K. M. (2012) · Journal of Cell Science · doi:10.1242/jcs.093708 · Cited by 219 · see citing works
“A recent study has shown that the induction of autophagy following ECM detachment is a prosurvival mechanism that prevents cells from undergoing anoikis (Fung et al., 2008).”
BackgroundTwo Faces of TGF-Beta1 in Breast Cancer
Zarzynska, J. M. (2014) · Mediators of Inflammation · doi:10.1155/2014/141747 · Cited by 214 · see citing works
The Diabetes Susceptibility Gene Clec16a Regulates Mitophagy
Soleimanpour, S. A., Gupta, A., Bakay, M., Ferrari, A. M., Groff, D. N., Fadista, J., Spruce, L. A., Kushner, J. A., Groop, L., Seeholzer, S. H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.016 · Cited by 211 · see citing works
Mechanisms and context underlying the role of autophagy in cancer metastasis
Dower, C. M., Wills, C. A., Frisch, S. M., & Wang, H. (2018) · Autophagy · doi:10.1080/15548627.2018.1450020 · Cited by 195 · see citing works
Autophagy and epithelial–mesenchymal transition: an intricate interplay in cancer
Gugnoni, M., Sancisi, V., Manzotti, G., Gandolfi, G., & Ciarrocchi, A. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.415 · Cited by 195 · see citing works
“The same authors also demonstrate that stable silencing of ATG5 or ATG7 enhances apoptosis and inhibits luminal colonization in a 3D culture model of MCF-10A breast cancer cells.(24) Autophagy activation is also a general mechanism that cancer cells use to overcome the potential stress induced by hyper-activated tyros…”
BackgroundLiu, H., He, Z., von Rütte, T., Yousefi, S., Hunger, R. E., & Simon, H.-U. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005864 · Cited by 188 · see citing works
Autophagy in disease: a double-edged sword with therapeutic potential
Martinet, W., Agostinis, P., Vanhoecke, B., Dewaele, M., & de Meyer, G. R. Y. (2009) · Clinical Science · doi:10.1042/cs20080508 · Cited by 186 · see citing works
Regulation of Autophagy by Kinases
Sridharan, S., Jain, K., & Basu, A. (2011) · Cancers · doi:10.3390/cancers3022630 · Cited by 182 · see citing works
“For example, autophagy has been shown to cause resistance to chemotherapeutic drugs [33], mediate anti-estrogen resistance [34] and resistance against detachment-induced cell death in breast cancer [35].”
BackgroundAutophagy-Regulating microRNAs and Cancer
Gözüaçık, D., Akkoç, Y., Öztürk, D. G., & Koçak, M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00065 · Cited by 172 · see citing works
Méresse, S., Fodil, M., Fleury, F., & Chénais, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239273 · Cited by 171 · see citing works
Autophagy in cellular growth control
Wang, R. C., & Levine, B. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.009 · Cited by 169 · see citing works
“In addition, the loss of EGFR signaling or substrate detachment results in the induction of autophagy in breast epithelial cells [16].”
BackgroundAutophagy as a mediator of chemotherapy-induced cell death in cancer
Notte, A., Leclère, L., & Michiels, C. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.015 · Cited by 167 · see citing works
“demonstrated using breast cancer cells in vitro [34].”
BackgroundRegulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK
Avivar‐Valderas, A., Bobrovnikova-Marjon, E. V., Diehl, J. A., Bardeesy, N. M., Debnath, J., & Aguirre‐Ghiso, J. A. (2012) · Oncogene · doi:10.1038/onc.2012.512 · Cited by 163 · see citing works
Self-citationDormancy and cancer stem cells: An enigma for cancer therapeutic targeting.
Talukdar, S., Bhoopathi, P., Emdad, L., Das, S. K., Sarkar, D., & Fisher, P. (2019) · Advances in Cancer Research · doi:10.1016/bs.acr.2018.12.002 · Cited by 141 · see citing works
Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis
Cabrera, S., Maciel, M., Herrera, I., Nava, T., Vergara, F., Gaxiola, M., López-Otín, C., Selman, M., & Pardo, A. (2015) · Autophagy · doi:10.1080/15548627.2015.1034409 · Cited by 163 · see citing works
NBR1 enables autophagy-dependent focal adhesion turnover
Kenific, C. M., Stehbens, S. J., Goldsmith, J., Leidal, A. M., Faure, N., Ye, J., Wittmann, T., & Debnath, J. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201503075 · Cited by 163 · see citing works
Self-citationKilling a cancer: what are the alternatives?
Kreuzaler, P. A., & Watson, C. J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3264 · Cited by 162 · see citing works
Autophagy and EMT in cancer and metastasis: Who controls whom?
Gundamaraju, R., Lu, W., Paul, M. K., Jha, N. K., Gupta, P. K., Ojha, S. K., Chattopadhyay, I., Pasupuleti, V. R., & Ghavami, S. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166431 · Cited by 163 · see citing works
Extracellular matrix regulation of autophagy
Lock, R., & Debnath, J. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.05.002 · Cited by 160 · see citing works
Self-citationDecuypere, J.-P., Welkenhuyzen, K., Luyten, T., Ponsaerts, R., Dewaele, M., Molgó, J., Agostinis, P., Missiaen, L., De Smedt, H., Parys, J. B., et al. (2011) · Autophagy · doi:10.4161/auto.7.12.17909 · Cited by 159 · see citing works
Roy, S., Leidal, A. M., Ye, J., Ronen, S. M., & Debnath, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.020 · Cited by 151 · see citing works
“Recent work demonstrates that TBC1D5 can shuttle between the retromer complex and LC3+ autophagosomes during starvation (Popovic et al., 2012), but the physiological functions for this RabGAP in endosomal-autophagy crosstalk have not been fully delineated.”
InfluentialSelf-citationThe role of autophagy induced by tumor microenvironment in different cells and stages of cancer
Yang, X. F., Yu, D., Yan, F., Jing, Y., Han, Z., Sun, K., Liang, L., Hou, J., & Wei, L. (2015) · Cell & Bioscience · doi:10.1186/s13578-015-0005-2 · Cited by 153 · see citing works
“Depletion of human ATGs, such as ATG5, ATG6 and ATG7, by si-RNA inhibits matrix detachment-induced autophagy [65].”
BackgroundGudipaty, S. A., Conner, C. M., Rosenblatt, J., & Montell, D. J. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060748 · Cited by 145 · see citing works
“Aside from using autophagy in response to metabolic stress to promote survival and resistance to anoikis (Fung et al. 2008), many aggressive cancers have adopted differential signaling to bypass anoikis and survive in places that normal cells cannot.”
BackgroundMalignant Precursor Cells Pre-Exist in Human Breast DCIS and Require Autophagy for Survival
Espina, V. A., Mariani, B. D., Gallagher, R. I., Tran, K., Banks, S., Wiedemann, J., Huryk, H., Mueller, C., Adamo, L., Deng, J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010240 · Cited by 144 · see citing works
“The second link is anoikis, the triggering of apoptotic cell death for cells that have been separated from their normal adhesion substratum [32].”
BackgroundKhan, S. U., Fatima, K., & Malik, F. A. (2022) · Clinical & Experimental Metastasis · doi:10.1007/s10585-022-10172-9 · Cited by 142 · see citing works
Dual functions of autophagy in the response of breast tumor cells to radiation
Bristol, M. L., Di, X. M., Beckman, M. J., Wilson, E. N., Henderson, S. C., Maiti, A., Fan, Z., & Gewirtz, D. A. (2012) · Autophagy · doi:10.4161/auto.19313 · Cited by 140 · see citing works
Roy, S., & Debnath, J. (2010) · Seminars in Immunopathology · doi:10.1007/s00281-010-0213-0 · Cited by 138 · see citing works
“showed that autophagy is induced in non-transformed cells following matrix detachment which protects cells from anoikis [80].”
Self-citationIntegrins and Cell Metabolism: An Intimate Relationship Impacting Cancer
Ata, R., & Antonescu, C. N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010189 · Cited by 133 · see citing works
“Several studies have noted a role for AMPK in mediating resistance to anoikis upon matrix detachment [120,215,216].”
BackgroundMechanism of autophagic regulation in carcinogenesis and cancer therapeutics
Panda, P. K., Mukhopadhyay, S., Das, D. N., Sinha, N., Naik, P. P., & Bhutia, S. K. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.02.013 · Cited by 137 · see citing works
Ng, T. L., Leprivier, G., Robertson, M. D., Chow, C., Martin, M. J., Laderoute, K. R., Davicioni, E., Triche, T. J., & Sorensen, P. H. B. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.119 · Cited by 135 · see citing works
“Mammary epithelial cells activate macroautophagy in response to detachment to suppress anoikis.(10) Detached non-transformed cells have reduced ATP levels, and oncogenic transformation reduces energy stress through modulation of glucose uptake and reactive oxygen species.”
BackgroundResultInfluentialDou, Z., Pan, J.-A., Dbouk, H. A., Ballou, L. M., DeLeon, J. L., Fan, Y., Chen, J.-S., Liang, Z., Li, G., Backer, J., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.022 · Cited by 130 · see citing works
Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells
Salimi, L., Akbari, A., Jabbari, N., Mojarad, B., Vahhabi, A., Szafert, S., Kalashani, S. A., Soraya, H., Nawaz, M., & Rezaie, J. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00426-y · Cited by 129 · see citing works
Yeo, S. K., Wen, J., Chen, S., & Guan, J. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2946 · Cited by 129 · see citing works
“Autophagy promotes resistance to anoikis, a trait that is important for the survival of tumor cells that have detached and are circulating (15, 16).”
BackgroundAntioxidant Enzymes Mediate Survival of Breast Cancer Cells Deprived of Extracellular Matrix
Davison, C. A., Durbin, S., Thau, M. R., Zellmer, V. R., Chapman, S. E., Diener, J. M., Wathen, C. A., Leevy, W. M., & Schafer, Z. T. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2482 · Cited by 124 · see citing works
MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells
Talukdar, S., Pradhan, A. K., Bhoopathi, P., Shen, X., August, L. A., Windle, J. J., Sarkar, D., Furnari, F. B., Cavenee, W. K., Das, S. K., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1721650115 · Cited by 127 · see citing works
“Anoikis, is a form of apoptosis, triggered when cells detach from the ECM (6, 7) and the catabolic process of autophagy imparts anoikisresistance in solid tumors (29, 30).”
BackgroundCell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis
Ohsawa, S., Vaughen, J. P., & Igaki, T. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.009 · Cited by 123 · see citing works
“One intriguing escape route from anoikis is by activating autophagy to survive via cellular selfcannibalization (Fung et al., 2008).”
Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde?
Zhou, S., Zhao, L., Kuang, M., Zhang, B., Liang, Z., Yi, T., Wei, Y., & Zhao, X. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.02.017 · Cited by 124 · see citing works
“igenesis [53].”
Zhao, H., Yang, M., Zhao, J., Wang, J., Zhang, Y., & Zhang, Q. (2013) · Medical Oncology · doi:10.1007/s12032-013-0475-1 · Cited by 124 · see citing works
“[9] found that autophagy-protected epithelial cancer cells from anoikis which was referred to the death of cancer cell due to detachment from the extracellular matrix.”
BackgroundAutophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression
Marsh, T., Kenific, C. M., Suresh, D., Velozo, H. G., Shamir, E. R., Mei, W., Tankka, A. T., Leidal, A. M., Kalavacherla, S., Woo, K., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.01.025 · Cited by 123 · see citing works
“In recent years, numerous in vitro studies implicate autophagy in supporting prometastatic behavior of tumor cells such as adhesionindependent survival, metabolic adaptation, and cell invasion and motility (Fung et al., 2008; Galavotti et al., 2013; Kenific et al., 2016; Rabinowitz and White, 2010).”
BackgroundSelf-citationAutophagy, Stress, and Cancer Metabolism: What Doesn't Kill You Makes You StrongerPreprint
Mathew, R., & White, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2012.76.011015 · Cited by 123 · see citing works
“Human cancer cell lines with endogenous K-Ras mutations activate autophagy upon extracellular matrix (ECM) detachment, which protects them from detachment-induced cell death (anoikis) (Fung et al. 2008).”
BackgroundAutophagy in tumour cell death
Macintosh, R. L., & Ryan, K. M. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.05.006 · Cited by 122 · see citing works
- Authors
- Fung, C., Lock, R., Gao, S., Salas, E., & Debnath, J.
- Affiliations
- University of California, San Francisco (US)
- Harvard University (US)
- *Department of Pathology and
- ORCID
- Debnath, Jayanta
- Venue
- Molecular Biology of the Cell
- Published
- 2008-03
- Volume
- 19
- Issue
- 3
- Pages
- 797-806
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2262959
- OpenAlex
- W2039403501
- Cited by
- 558
- References
- 52
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 15 · 2023: 26 · 2022: 33 · 2021: 45 · 2020: 41 · 2019: 35 · 2018: 36 · 2017: 23 · 2016: 40 · 2015: 37 · 2014: 44 · 2013: 43 · 2012: 28
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Association for Cancer Research
- National Institutes of Health
- Genentech
- University of California, San Francisco
- National Cancer Institute (K08CA098419)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- autophagy, anoikis, extracellular matrix detachment, lumen formation, epithelial morphogenesis, apoptosis, Bcl-2, ATG5, ATG7, clonogenic survival, autophagy-related genes, mammary tumor cells
- MeSH terms
- Autophagy-Related Protein 5, Autophagy-Related Protein 7, Animals, Autophagy, Cell Adhesion, Cell Line, Cell Survival, Dogs, Epidermal Growth Factor, Epithelial Cells, Extracellular Matrix, Fibroblasts, Humans, Microtubule-Associated Proteins, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Ubiquitin-Activating Enzymes, Mice, ErbB Receptors
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
