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Signalling mechanisms of anoikis M. Zhan, H. Zhao and Z.C. Han State key Laboratory of Experimental Hematology, Institute of Hematology, National Research Center of Stem Cell Engineering and Technology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union of Medical College, Tianjin, China Offprint requests to: Dr. Mei Zhan, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 30020, China, Fax: 86 22 27235092. e-mail: meizsky@hotmail.com
Summary. Apoptosis following loss of cell anchorage ('anoikis') is of relevance for development, tissue homeostasis and disease. Integrins regulate cell viability through their interaction with the extracellular matrix and they can sense mechanical forces arising from the matrix and convert these stimuli to chemical signals capable of modulating intracellular signal transduction. Recently it has been shown that protein kinase signalling pathways and apoptosis-related molecular control anoikis both positively and negatively. Focal adhesion kinase, when activated by integrins, can suppress anoikis. Phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase may mediate the anoikis-suppressing effects of cells. Conversely, the stress-activated protein kinase/Jun amino-terminal kinase pathway promotes anoikis. In addition, certain bcl-2 and bcl-2-related proteins may also participate in the regulating of anoikis. In this review, molecular mechanisms of signal pathway inducing and perpetuating detachment-induced apoptosis will be discussed with special emphasis on the role of integrins, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase and bcl-2 family members. Histol. Histopathol. 19, 973-983 (2004) Key words: Anoikis,
Integrin, Extracellular matrix, Focal adhesion kinase, Phosphoinositide-3
kinase, Mitogen-activated protein kinase, bcl-2 |