Entosis: Cell-in-Cell Formation that Kills Through Entotic Cell Death
Abstract
Entosis is a cell-in-cell formation mechanism that targets viable cells for uptake in epithelial cell cultures and human tumors. Entotic cells control their own engulfment, by invading into their hosts in a Rho-GTPase and actomyosin-dependent manner. Although entotic cells are internalized while alive, most eventually undergo a non-apoptotic form of cell death, called entotic cell death, that is executed non-cell-autonomously by autophagy proteins and lysosomes. Here we review the current understanding of entosis and entotic cell death and discuss the potential roles of this process in cancer. Keywords: Cell-in-cell, entosis, entotic cell death, cannibalism, phagocytosis, engulfment, autophagy, LAP, cell competition.
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?
Entosis is a form of cell cannibalism occurring in healthy and malignant mammalian tissues, involving engulfment of viable cells by non-phagocytic cells of the same or a different type.
“Entosis is a form of cell cannibalism that occurs in healthy and malignant mammalian tissues, involving the engulfment of viable cells by non-phagocytic cells of the same (homotypic) or a different (heterotypic) type [691, 692].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [692]
Internalization in entosis is often but not always followed by demise of internalized cells.
“Often (but not always), internalization is followed by the demise of internalized cells (which are commonly referred to as “entotic cells”) [691–693].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [692]
Cites
1 retracted
Martinez, J., Almendinger, J., Oberst, A., Ness, R., Dillon, C. P., Fitzgerald, P., Hengartner, M. O., & Green, D. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113421108 · Cited by 655 · see citing works
RetractedToll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis
Sanjuan, M. A., Dillon, C. P., Tait, S. W. G., Moshiach, S., Dorsey, F., Connell, S., Komatsu, M., Tanaka, K., Cleveland, J. L., Withoff, S., et al. (2007) · Nature · doi:10.1038/nature06421 · Cited by 1,347 · see citing works
The autophagosome: origins unknown, biogenesis complex
Lamb, C. A., Yoshimori, T., & Tooze, S. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3696 · Cited by 1,307 · see citing works
Killing activity of neutrophils is mediated through activation of proteases by K+ flux
Reeves, E. P., Lu, H., Jacobs, H. L., Messina, C. G. M., Bolsover, S., Gabella, G., Potma, E. O., Warley, A., Roes, J., & Segal, A. W. (2002) · Nature · doi:10.1038/416291a · Cited by 1,153 · see citing works
A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion
Overholtzer, M., Mailleux, A. A., Mouneimne, G., Normand, G., Schnitt, S. J., King, R. W., Cibas, E. S., & Brugge, J. S. (2007) · Cell · doi:10.1016/j.cell.2007.10.040 · Cited by 748 · see citing works
Self-citationActivation of antibacterial autophagy by NADPH oxidases
Huang, J., Canadien, V., Lam, G. Y., Steinberg, B. E., Dinauer, M. C., Magalhaes, M. A. O., Glogauer, M., Grinstein, S., & Brumell, J. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811045106 · Cited by 556 · see citing works
Florey, O., Kim, S. E., Sandoval, C. P., Haynes, C. M., & Overholtzer, M. (2011) · Nature Cell Biology · doi:10.1038/ncb2363 · Cited by 459 · see citing works
Self-citationMyc-driven endogenous cell competition in the early mammalian embryo
Claverı́a, C., Giovinazzo, G., Sierra, R., & Torres, M. (2013) · Nature · doi:10.1038/nature12389 · Cited by 370 · see citing works
Eaten alive! Cell death by primary phagocytosis: ‘phagoptosis’
Brown, G. C., & Neher, J. J. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.05.002 · Cited by 320 · see citing works
Competition between human cells by entosis
Sun, Q., Luo, T., Ren, Y., Florey, O., Shirasawa, S., Sasazuki, T., Robinson, D. N., & Overholtzer, M. (2014) · Cell Research · doi:10.1038/cr.2014.138 · Cited by 233 · 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
V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation
Florey, O., Gammoh, N., Kim, S. E., Jiang, X., & Overholtzer, M. (2014) · Autophagy · doi:10.4161/15548627.2014.984277 · Cited by 212 · see citing works
Self-citationThe cell biology of cell-in-cell structures
Overholtzer, M., & Brugge, J. S. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2504 · Cited by 202 · see citing works
Self-citationA non-genetic route to aneuploidy in human cancers
Krajcovic, M., Johnson, N. B., Sun, Q., Normand, G., Hoover, N., Yao, E., Richardson, A. L., King, R. W., Cibas, E. S., Schnitt, S. J., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2174 · Cited by 188 · see citing works
Self-citationEntosis Allows Timely Elimination of the Luminal Epithelial Barrier for Embryo Implantation
Li, Y., Sun, X., & Dey, S. K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.035 · Cited by 155 · see citing works
mTOR regulates phagosome and entotic vacuole fission
Krajcovic, M., Krishna, S., Akkari, L., Joyce, J. A., & Overholtzer, M. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-07-0408 · Cited by 149 · see citing works
Self-citationInduction of entosis by epithelial cadherin expression
Sun, Q., Cibas, E. S., Huang, H., Hodgson, L., & Overholtzer, M. (2014) · Cell Research · doi:10.1038/cr.2014.137 · Cited by 148 · see citing works
Self-citationAutophagy proteins in macroendocytic engulfment
Florey, O., & Overholtzer, M. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.04.005 · Cited by 132 · see citing works
Self-citationLam, G. Y., Cemma, M., Muise, A. M., Higgins, D. E., & Brumell, J. H. (2013) · Autophagy · doi:10.4161/auto.24406 · Cited by 125 · see citing works
Regulation of Phagocytosis by Rho GTPases
Niedergang, F., & Chavrier, P. (2005) · Current topics in microbiology and immunology · doi:10.1007/3-540-27511-8_4 · Cited by 124 · see citing works
Mechanisms of Ploidy Increase in Human Cancers: A New Role for Cell Cannibalism
Krajcovic, M., & Overholtzer, M. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3127 · Cited by 102 · see citing works
Self-citationLuo, T., Mohan, K., Srivastava, V., Ren, Y., Iglesias, P. A., & Robinson, D. N. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2011.12.020 · Cited by 88 · see citing works
A mechanosensory system governs myosin II accumulation in dividing cells
Kee, Y.-S., Ren, Y., Dorfman, D., Iijima, M., Firtel, R., Iglesias, P. A., & Robinson, D. N. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-07-0601 · Cited by 68 · see citing works
G-protein-coupled receptor signaling and polarized actin dynamics drive cell-in-cell invasion
Purvanov, V., Holst, M., Khan, J., Baarlink, C., & Grosse, R. (2014) · eLife · doi:10.7554/elife.02786 · Cited by 67 · see citing works
Wang, S., Mf, H., Yh, C., My, W., Xm, Y., Bai, J., Hy, Z., Wang, Y.-Y., Zhao, H., Mei, Q., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.352 · Cited by 66 · see citing works
Aurora A orchestrates entosis by regulating a dynamic MCAK–TIP150 interaction
Xia, P., Zhou, J., Song, X., Wu, B., Liu, X., Li, D., Zhang, S., Wang, Z., Yu, H., Ward, T. L., et al. (2014) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mju016 · Cited by 57 · see citing works
Wang, M., Ning, X., Chen, A., Huang, H., Ni, C., Zhou, C., Yu, K., Lan, S., Wang, Q., Li, S., et al. (2015) · Scientific Reports · doi:10.1038/srep12223 · Cited by 54 · see citing works
Ishikawa, F., Ushida, K., Mori, K., & Shibanuma, M. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.583 · Cited by 53 · see citing works
Entosis, a key player in cancer cell competition
Kroemer, G., & Perfettini, J. (2014) · Cell Research · doi:10.1038/cr.2014.133 · Cited by 49 · see citing works
Autophagy proteins regulate cell engulfment mechanisms that participate in cancer
Kim, S. E., & Overholtzer, M. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.05.004 · Cited by 35 · see citing works
Self-citationWen, S., Shang, Z., Zhu, S., Chang, C., & Niu, Y. (2013) · The Prostate · doi:10.1002/pros.22676 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationThe pancreatic cancer genome revisited
Hayashi, A., Hong, J., & Iacobuzio-Donahue, C. A. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00463-z · Cited by 211 · see citing works
Autophagy and endocytosis – interconnections and interdependencies
Birgisdottir, Å. B., & Johansen, T. (2020) · Journal of Cell Science · doi:10.1242/jcs.228114 · Cited by 170 · see citing works
Mechanisms and consequences of entosis
Krishna, S., & Overholtzer, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2207-0 · Cited by 118 · see citing works
Self-citationPreliminary evidence for the presence of multiple forms of cell death in diabetes cardiomyopathy
Wei, J., Zhao, Y., Liang, H., Du, W., & Wang, L. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.08.026 · Cited by 106 · see citing works
Cancer cell cannibalism: Multiple triggers emerge for entosis
Durgan, J., & Florey, O. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.03.004 · Cited by 83 · see citing works
Self-citationDisulfidptosis: A new type of cell death
Xiao, F., Li, H., Yang, B., Che, H., Xu, F., Li, G., Zhou, C., & Wang, S. (2024) · APOPTOSIS · doi:10.1007/s10495-024-01989-8 · Cited by 84 · see citing works
Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment
Hawk, M. A., & Schafer, Z. T. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000260 · Cited by 80 · see citing works
A guide to membrane atg8ylation and autophagy with reflections on immunity
Deretic, V. P., & Lazarou, M. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202203083 · Cited by 78 · see citing works
Liu, X., Yang, W., Guan, Z.-Z., Yu, W., Fan, B., Xu, N., & Liao, D. J. (2018) · Cell & Bioscience · doi:10.1186/s13578-018-0206-6 · Cited by 64 · see citing works
Wang, X., Li, Y., Li, J., Li, L., Zhu, H., Chen, H., Kong, R., Wang, G., Wang, Y., Hu, J., et al. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00311 · Cited by 53 · see citing works
MRTF transcription and Ezrin-dependent plasma membrane blebbing are required for entotic invasion
Hinojosa, L. S., Holst, M., Baarlink, C., & Grosse, R. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201702010 · Cited by 41 · see citing works
Macropinocytosis and autophagy crosstalk in nutrient scavenging
Florey, O., & Overholtzer, M. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0154 · Cited by 38 · see citing works
Self-citationRho-ROCK signaling mediates entotic cell death in tumor
Zeng, C., Zeng, B., Dong, C., Liu, J., & Xing, F. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-0238-7 · Cited by 38 · see citing works
Mechanisms and significance of entosis for tumour growth and progression
Gaptulbarova, K. A., Tsydenova, I. A., Dolgasheva, D. S., Kravtsova, E. A., Ibragimova, M. K., Vtorushin, S. V., & Литвяков, Н. В. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01877-9 · Cited by 35 · see citing works
Entosis: the core mechanism and crosstalk with other cell death programs
Kim, S.-H., Lee, D., Kim, S. E., & Overholtzer, M. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01227-w · Cited by 35 · see citing works
Self-citationDemin, S. Y., Berdieva, M. A., & Goodkov, A. V. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.005 · Cited by 28 · see citing works
N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential
Wu, Q., Fu, X., Liu, G., He, X., Li, Y., & Ou, C. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01665-7 · Cited by 29 · see citing works
Cell death classification: A new insight based on molecular mechanisms
Dehghan, S., Kheshtchin, N., Hassannezhad, S., & Soleimani, M. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113860 · Cited by 18 · see citing works
Zhao, C. (2025) · Discover Oncology · doi:10.1007/s12672-025-02022-3 · Cited by 17 · see citing works
Ojasalu, K., Lieber, S., Sokòl, A. M., Nist, A., Stiewe, T., Bullwinkel, I., Finkernagel, F., Reinartz, S., Müller‐Brüsselbach, S., Grosse, R., et al. (2023) · Theranostics · doi:10.7150/thno.81656 · Cited by 17 · see citing works
Zhang, X., Zhang, M., Song, L., Wang, S., Wei, X., Shao, W., & Song, N. (2023) · Scientific Reports · doi:10.1038/s41598-023-46577-z · Cited by 16 · see citing works
Navigating the complexities of cell death: Insights into accidental and programmed cell death
Lotfi, M.-S., & Rassouli, F. B. (2024) · Tissue and Cell · doi:10.1016/j.tice.2024.102586 · Cited by 15 · see citing works
Transcriptomic features of programmed and inflammatory cell death in gingival tissues
Ebersole, J. L., Kirakodu, S. S., Nguyen, L. M., & González, O. A. (2024) · Oral Diseases · doi:10.1111/odi.14939 · Cited by 12 · see citing works
Sorokin, O., Hause, F., Wedler, A., Alakhras, T., Bauchspiess, T., Dietrich, A., Günther, W. F., Guha, C., Obika, K. B., Kraft, J., et al. (2025) · APOPTOSIS · doi:10.1007/s10495-025-02161-6 · Cited by 11 · see citing works
Sphingolipid metabolism and regulated cell death in malignant melanoma
Yan, K., Zhang, W., Song, H., & Xu, X. (2024) · APOPTOSIS · doi:10.1007/s10495-024-02002-y · Cited by 8 · see citing works
Autophagic cell death in viral infection: Do TAM receptors play a role?
Datan, E., & Salman, S. (2020) · International review of cytology · doi:10.1016/bs.ircmb.2020.10.001 · Cited by 5 · see citing works
Cell-in-cell phenomena across the tree of life
Kapsetaki, S. E., Cisneros, L. H., & Maley, C. C. (2024) · Scientific Reports · doi:10.1038/s41598-024-57528-7 · Cited by 5 · see citing works
Identification of Novel Potential Genes Involved in Cancer by Integrated Comparative Analyses
Monticolo, F., Palomba, E., & Chiusano, M. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249560 · Cited by 4 · see citing works
Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics
Liu, Y., Chen, Q., Xu, J., & Chi, H. (2026) · APOPTOSIS · doi:10.1007/s10495-026-02298-y · Cited by 4 · see citing works
Mechanistic paradigms of cell death - revisited
Rana, S. V. S. (2021) · Journal of Environmental Biology · doi:10.22438/jeb/42/4/mrn-1965 · Cited by 3 · see citing works
A reliable elasticity sensing method for analysis of cell entosis using microfluidic cytometer
Ren, J., & Fan, L. (2023) · Biomedical Engineering Letters · doi:10.1007/s13534-023-00264-0 · Cited by 3 · see citing works
Zhou, C., & Bai, Y. (2025) · ImmunoTargets and Therapy · doi:10.2147/itt.s555950 · Cited by 2 · see citing works
Gou, Z.-H., Su, N., Li, X., Ren, D.-P., Ren, S.-S., Wang, L., & Wang, Y. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1580355 · Cited by 2 · see citing works
Do Marine Polysaccharides Carrageenans Modulate Non-apoptotic Regulated Cell Deaths ? (a Review)
Tkachenko, A. S., Onishchenko, A. I., & Prokopіuk, V. (2023) · Current Pharmacology Reports · doi:10.1007/s40495-023-00339-7 · Cited by 2 · see citing works
Evolving methodologies for identification and differentiation of regulated cell death modalities
Kaur, A., Urvi, Pandey, R. K., & Mehrotra, S. (2025) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2025.06.023 · Cited by 1 · see citing works
Chen, Y., Li, M., Li, Z., Lin, X., Xu, Y., Qu, S., Lv, M., Liao, M., Zhang, L., Yang, Q., et al. (2026) · Forensic Science International Reports · doi:10.1016/j.fsir.2026.100452 · Cited by 1 · see citing works
Zhang, C., & Shen, C. (2023) · Medicine · doi:10.1097/md.0000000000035881 · Cited by 1 · see citing works
Cancer Metastasis, ROS/Redox Signaling, and PCD Resistance/Redox Metabolism
Bansal, M. P. (2023) · Springer eBooks · doi:10.1007/978-981-99-7342-2_5 · Cited by 1 · see citing works
ROS/Redox Signaling and Apoptosis/Necroptosis/Autophagy in Cancer
Bansal, M. P. (2023) · Springer eBooks · doi:10.1007/978-981-99-7342-2_4
Wu, C., Fang, S., Wu, L., Mi, Z., Yao, Y., Liao, Y., Zhao, Y., Wang, T., & Na, J. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01580-8
Life of the cell: Is it important how cells die?
Kravic‐Stevovic, T., Martinović, T., Ćirić, D., Rakočević, J., Paunković, I., Zaletel, I. V., Despotović, S. Z., Ćetković, M., & Bumbasirevic, V. Z. (2025) · Medicinska istrazivanja · doi:10.5937/medi58-54467
Comprehensive analysis of the role of diverse programmed cell death patterns in sepsis
Yu, X., Zhou, Z., Ma, J., Wang, X., Zhao, C., Hou, A., & Sun, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1685533
Correlation of Cell‐in‐Cell Structure With Prognosis in Solid Tumors—A Meta‐Analysis
Zi, H., Dai, Y., Li, M., Wang, Y., Wang, M., Wang, S., Bai, Y., Sun, J., Fan, C., Ding, J., et al. (2025) · BioMed Research International · doi:10.1155/bmri/4943372
Potapov, A. L., Spashchanskii, R., Kazakov, A., Shepeleva, A. A., Lisitsa, U., Bugrova, M. L., & Николаевна, Д. И. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15120591
- Authors
- Florey, O., Kim, S., & Overholtzer, M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Current Molecular Medicine
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-11-05
- Volume
- 15
- Issue
- 9
- Pages
- 861-866
- ISSN
- 1566-5240 (ISSN-L)
- OpenAlex
- W2160733843
- Cited by
- 45
- References
- 31
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 1
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (16337)
- National Cancer Institute (R01CA154649)
- 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 › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- entosis, cell cannibalism, phagocytosis, autophagy, lysosomes, Rho GTPases, actomyosin, cell competition, cancer
- MeSH terms
- Animals, Humans, Cell Death, Apoptosis, Entosis
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
