Signalling mechanisms of anoikis.
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.
Zhan
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State key Laboratory of Experimental Hematology, Institute of Hematology, National Research Center of Stem Cell Engineering and Technology, Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Tianjin, China. meizsky@hotmail.com
Zhao
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H
Han
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ZC
D000818:Animals; D023102:Anoikis; D005109:Extracellular Matrix / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
D016023:Integrins; D019253:Proto-Oncogene Proteins c-bcl-2; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases