AI Article Synopsis
- The study investigates how the PAK1 kinase contributes to cancer development and cell survival, particularly in lung cancer, and reveals its regulation remains unclear.
- It was found that irradiation of lung cancer cells led to the upregulation and phosphorylation of PAK1, which is necessary for its stability and for interacting with a protein called Snail.
- Using JAK2 inhibitors showed potential to enhance the effectiveness of radiation therapy by blocking the epithelial-mesenchymal transition (EMT), suggesting these inhibitors could be a promising treatment for lung cancer.
Article 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.
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| http://dx.doi.org/10.1158/0008-5472.CAN-14-0735 | DOI Listing |
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