Beyond structure, to survival: activation of Stat3 by cadherin engagement.
Cells in normal tissues or in tumors have extensive opportunities for adhesion to their neighbors and the importance of cell to cell contact in the study of fundamental cellular processes is beginning to emerge. In this review, we discuss recent evidence of dramatic changes in the activity of an important signal transducer found to be profoundly affected by cell to cell adhesion, the signal transducer and activator of transcription-3 (Stat3). Direct cadherin engagement, growth of cells to postconfluence, or formation of multicellular aggregates were found to induce a striking increase in the levels of Stat3 activity, Rac1/Cdc42, and members of the IL6 receptor family in different settings. This activation was specific to Stat3, in that the levels of the extracellular signal regulated kinase (Erk1/2), a signal transducer often coordinately activated with Stat3 by a number of growth factors or oncogenes, remained unaffected by cell density. Density-dependent Stat3 activation may play a key role in survival, and could contribute to the establishment of cell polarity. It is clear that at any given time the total Stat3 activity levels in a cell are the sum of the effects of cell to cell adhesion plus the conventional Stat3 activating factors present.
Raptis
Leda
L
Department of Microbiology and Immunology, and Cancer Research Institute, Queen's University, Kingston, ON K7L 3N6. raptis1@queensu.ca
Arulanandam
Rozanne
R
Vultur
Adina
A
Geletu
Mulu
M
Chevalier
Sébastien
S
Feracci
Hélène
H
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D053613:Janus Kinase 1; D020830:rac1 GTP-Binding Protein