In normal tissues or tumors, cells have extensive opportunities for adhesion to their neighbors. This state is mimicked by dense cell cultures. In this review, we integrate some recent findings on a key signal transducer, STAT3 (signal transducer and activator of transcription-3), whose activity is dramatically increased following cadherin-mediated cell to cell adhesion. Cadherin engagement, favored in dense cell cultures, causes a dramatic increase in total Rac/Cdc42 protein levels through inhibition of proteasomal degradation, which is followed by activation of IL-6 and STAT3. The cadherin/Rac/IL-6/STAT3 axis offers a potent survival signal that is a prerequisite for neoplastic transformation, as well as normal tissue function.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891631PMC
http://dx.doi.org/10.4161/jkst.27363DOI Listing

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