Journal
CELL CYCLE
Volume 7, Issue 11, Pages 1613-1622Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.7.11.5952
Keywords
midkine; Notch2; Jak2; Stat3; shRNA; immortalized HaCaT keratinocytes; squamous cell carcinomas; EMT; epithelial-to-mesenchymal transition
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Epithelial-to-mesenchymal transition (EMT) underlies cell plasticity and embryonic development and is frequently observed in advanced tumorigenesis. We demonstrated that midkine (MK), a retinoic acid-inducible heparin-binding mitogen, promotes EMT in immortalized HaCaT keratinocytes. We showed that MK binds to the Notch2 receptor in HaCaT keratinocytes. We further found that MK activates Notch2 signaling leading to protein/protein interactions between Hes1 and Jak2/Stat3 intermediates. We thus suggest that MK-induced cross talk of Notch2/Jak2/Stat3 signaling pathways can regulate cell plasticity and motility contributing to the EMT and later stages of tumorigenesis.
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