Abstract:
:The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in tumorigenesis and cell survival in many cancers, but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was essential for PAK1 protein stability and binding to Snail. This radiation-induced JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition (EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2 inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, with additional implications for the use of JAK2 inhibitors as radiosensitizers in lung cancer treatment.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kim E,Youn H,Kwon T,Son B,Kang J,Yang HJ,Seong KM,Kim W,Youn Bdoi
10.1158/0008-5472.CAN-14-0735subject
Has Abstractpub_date
2014-10-01 00:00:00pages
5520-31issue
19eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-0735journal_volume
74pub_type
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