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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Anoikis


High impact information on Anoikis


Chemical compound and disease context of Anoikis


Biological context of Anoikis

  • The central problem of anoikis is to understand how integrin-mediated cell adhesion signals control the apoptotic machinery [13].
  • Bim is strongly induced after cell detachment and downregulation of Bim expression by RNA interference (RNAi) inhibits anoikis [14].
  • CONCLUSIONS: Distinct p38 isoforms play a major role in the induction of enterocytic anoikis and the regulation of such selective p38 isoform-mediated anoikis is linked with the state of cell differentiation [15].
  • Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells [16].
  • Pgrn stimulates the invasion of SW-13 cells across Matrigel-coated filters, increases the expression of matrix metalloproteinase 13 and 17, protects against anoikis, and overcomes the inhibition of cell growth imposed on SW-13 cells by interstitial type-I collagen [17].

Anatomical context of Anoikis


Associations of Anoikis with chemical compounds

  • Another early response to cell suspension was the activation of the ICE-related cysteine protease, ICE/LAP3; this activation and anoikis were suppressed by the ICE-protease inhibitor, crmA [22].
  • The insulin-like growth factor I receptor is required for Akt activation and suppression of anoikis in cells transformed by the ETV6-NTRK3 chimeric tyrosine kinase [23].
  • Unexpectedly, oncogenic Ras failed to activate Akt, and treatment of Ras-transformed RIE-1 cells with the LY294002 PI3K inhibitor did not affect anoikis resistance or growth in soft agar [24].
  • Here we demonstrate that G(1)/S arrest by overexpression of the cyclin-dependent kinase inhibitors p16(INK4a), p21(Cip1), or p27(Kip1) or by treatment with mimosine or aphidicolin confers anoikis resistance in MCF-10A cells [25].
  • Tyrosine kinase inhibitor genistein rendered three of them sensitive to anoikis [3].

Gene context of Anoikis

  • Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis [14].
  • Resistance to anoikis correlated with PKB/Akt activation in suspension, but not with changes in PTEN or p110alpha PI3 kinase levels [26].
  • Surprisingly, we found that ERK and phosphatidylinositol 3'-kinase/AKT activation did not have significant roles in conferring anoikis resistance [27].
  • Human carcinoembryonic antigen functions as a general inhibitor of anoikis [28].
  • The IGF-I signal recovered by MMP-7 protected against apoptosis induced by anoikis in 3T3-IGF-IR cells [29].

Analytical, diagnostic and therapeutic context of Anoikis

  • Using gene silencing and gene transfer techniques, we show that increased expression of the apoptosis inhibitory protein XIAP contributes to anoikis resistance of the circulating metastatic human prostate carcinoma cells [30].
  • Western blot analysis demonstrated that neither p53 nor Bcl-2, Bcl-XL and Bax protein expression changed during anoikis [31].
  • The signaling events culminating in anoikis are still unclear; recent studies have implicated Stress Activated Protein Kinase (SAPK), also known as Jun-N-Terminal kinase, as a potentially crucial signal transducer and mediator of anoikis [32].
  • Expression of KLF5 in TE2 cells inhibits proliferation, and both KLF4 and KLF5 decrease viability after treatment with hydrogen peroxide and increase anoikis [33].


  1. The neurotrophic receptor TrkB in anoikis resistance and metastasis: a perspective. Geiger, T.R., Peeper, D.S. Cancer Res. (2005) [Pubmed]
  2. The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Emberley, E.D., Niu, Y., Curtis, L., Troup, S., Mandal, S.K., Myers, J.N., Gibson, S.B., Murphy, L.C., Watson, P.H. Cancer Res. (2005) [Pubmed]
  3. Tyrosine kinase-dependent, phosphatidylinositol 3'-kinase, and mitogen-activated protein kinase-independent signaling pathways prevent lung adenocarcinoma cells from anoikis. Wei, L., Yang, Y., Yu, Q. Cancer Res. (2001) [Pubmed]
  4. Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B. Zeng, Q., Chen, S., You, Z., Yang, F., Carey, T.E., Saims, D., Wang, C.Y. J. Biol. Chem. (2002) [Pubmed]
  5. CD99 acts as an oncosuppressor in osteosarcoma. Manara, M.C., Bernard, G., Lollini, P.L., Nanni, P., Zuntini, M., Landuzzi, L., Benini, S., Lattanzi, G., Sciandra, M., Serra, M., Colombo, M.P., Bernard, A., Picci, P., Scotlandi, K. Mol. Biol. Cell (2006) [Pubmed]
  6. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Jan, Y., Matter, M., Pai, J.T., Chen, Y.L., Pilch, J., Komatsu, M., Ong, E., Fukuda, M., Ruoslahti, E. Cell (2004) [Pubmed]
  7. The regulation of anoikis: MEKK-1 activation requires cleavage by caspases. Cardone, M.H., Salvesen, G.S., Widmann, C., Johnson, G., Frisch, S.M. Cell (1997) [Pubmed]
  8. Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Puthalakath, H., Villunger, A., O'Reilly, L.A., Beaumont, J.G., Coultas, L., Cheney, R.E., Huang, D.C., Strasser, A. Science (2001) [Pubmed]
  9. Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas. Casanova, I., Parreño, M., Farré, L., Guerrero, S., Céspedes, M.V., Pavon, M.A., Sancho, F.J., Marcuello, E., Trias, M., Mangues, R. Int. J. Cancer (2006) [Pubmed]
  10. Anoikis induction by quinazoline based alpha 1-adrenoceptor antagonists in prostate cancer cells: antagonistic effect of bcl-2. Keledjian, K., Kyprianou, N. J. Urol. (2003) [Pubmed]
  11. Alpha 4 integrin increases anoikis of human osteosarcoma cells. Marco, R.A., Díaz-Montero, C.M., Wygant, J.N., Kleinerman, E.S., McIntyre, B.W. J. Cell. Biochem. (2003) [Pubmed]
  12. Doxazosin inhibits human vascular endothelial cell adhesion, migration, and invasion. Keledjian, K., Garrison, J.B., Kyprianou, N. J. Cell. Biochem. (2005) [Pubmed]
  13. Anoikis mechanisms. Frisch, S.M., Screaton, R.A. Curr. Opin. Cell Biol. (2001) [Pubmed]
  14. Integrins 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. Nat. Cell Biol. (2003) [Pubmed]
  15. Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis. Vachon, P.H., Harnois, C., Grenier, A., Dufour, G., Bouchard, V., Han, J., Landry, J., Beaulieu, J.F., Vézina, A., Dydensborg, A.B., Gauthier, R., Côté, A., Drolet, J.F., Lareau, F. Gastroenterology (2002) [Pubmed]
  16. Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells. Nishimura, S., Adachi, M., Ishida, T., Matsunaga, T., Uchida, H., Hamada, H., Imai, K. Cancer Res. (2001) [Pubmed]
  17. Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. He, Z., Ismail, A., Kriazhev, L., Sadvakassova, G., Bateman, A. Cancer Res. (2002) [Pubmed]
  18. Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Di-Poï, N., Tan, N.S., Michalik, L., Wahli, W., Desvergne, B. Mol. Cell (2002) [Pubmed]
  19. Matrix attachment regulates Fas-induced apoptosis in endothelial cells: a role for c-flip and implications for anoikis. Aoudjit, F., Vuori, K. J. Cell Biol. (2001) [Pubmed]
  20. Raf-MEK-Erk cascade in anoikis is controlled by Rac1 and Cdc42 via Akt. Zugasti, O., Rul, W., Roux, P., Peyssonnaux, C., Eychene, A., Franke, T.F., Fort, P., Hibner, U. Mol. Cell. Biol. (2001) [Pubmed]
  21. Nuclear hormone receptor NR4A2 is involved in cell transformation and apoptosis. Ke, N., Claassen, G., Yu, D.H., Albers, A., Fan, W., Tan, P., Grifman, M., Hu, X., Defife, K., Nguy, V., Meyhack, B., Brachat, A., Wong-Staal, F., Li, Q.X. Cancer Res. (2004) [Pubmed]
  22. A role for Jun-N-terminal kinase in anoikis; suppression by bcl-2 and crmA. Frisch, S.M., Vuori, K., Kelaita, D., Sicks, S. J. Cell Biol. (1996) [Pubmed]
  23. The insulin-like growth factor I receptor is required for Akt activation and suppression of anoikis in cells transformed by the ETV6-NTRK3 chimeric tyrosine kinase. Martin, M.J., Melnyk, N., Pollard, M., Bowden, M., Leong, H., Podor, T.J., Gleave, M., Sorensen, P.H. Mol. Cell. Biol. (2006) [Pubmed]
  24. Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase. McFall, A., Ulkü, A., Lambert, Q.T., Kusa, A., Rogers-Graham, K., Der, C.J. Mol. Cell. Biol. (2001) [Pubmed]
  25. G1/S cell cycle arrest provides anoikis resistance through Erk-mediated Bim suppression. Collins, N.L., Reginato, M.J., Paulus, J.K., Sgroi, D.C., Labaer, J., Brugge, J.S. Mol. Cell. Biol. (2005) [Pubmed]
  26. Switch from alphavbeta5 to alphavbeta6 integrin expression protects squamous cell carcinomas from anoikis. Janes, S.M., Watt, F.M. J. Cell Biol. (2004) [Pubmed]
  27. Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikis. Eckert, L.B., Repasky, G.A., Ulkü, A.S., McFall, A., Zhou, H., Sartor, C.I., Der, C.J. Cancer Res. (2004) [Pubmed]
  28. Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Ordoñez, C., Screaton, R.A., Ilantzis, C., Stanners, C.P. Cancer Res. (2000) [Pubmed]
  29. Matrix metalloproteinase-7 facilitates insulin-like growth factor bioavailability through its proteinase activity on insulin-like growth factor binding protein 3. Miyamoto, S., Yano, K., Sugimoto, S., Ishii, G., Hasebe, T., Endoh, Y., Kodama, K., Goya, M., Chiba, T., Ochiai, A. Cancer Res. (2004) [Pubmed]
  30. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Berezovskaya, O., Schimmer, A.D., Glinskii, A.B., Pinilla, C., Hoffman, R.M., Reed, J.C., Glinsky, G.V. Cancer Res. (2005) [Pubmed]
  31. Apoptosis induced by denied adhesion to extracellular matrix (anoikis) in thyroid epithelial cells is p53 dependent but fails to correlate with modulation of p53 expression. Vitale, M., Di Matola, T., Bifulco, M., Casamassima, A., Fenzi, G., Rossi, G. FEBS Lett. (1999) [Pubmed]
  32. Functional dissociation of anoikis-like cell death and activity of stress activated protein kinase. Krestow, J.K., Rak, J., Filmus, J., Kerbel, R.S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  33. KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells. Yang, Y., Goldstein, B.G., Chao, H.H., Katz, J.P. Cancer Biol. Ther. (2005) [Pubmed]
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