Cathepsin L promotes ionizing radiation-induced U251 glioma cell migration and invasion through regulating the GSK-3β/CUX1 pathway.
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Abstract | :
Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by tumor cells. Our previous study found that CTSL was involved in ionizing radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase of glioma invasion and migration. However, the mechanisms by which CTSL promoted this IR-induced glioma migration and invasion remained unclear. In this study, we demonstrated that IR reduced glycogen synthase kinase-3β (GSK-3β) activity, via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells. Moreover, inhibition of p-GSK-3βSer9 in overexpressing CTSL cells attenuated EMT and decreased the expression of snail, an EMT-related transcription factor. As a result U251 cell migration and invasion was inhibited compared to over-CTSL cells. Alternatively, when CTSL was activated by IR or exogenously overexpressed, CTSL promoted EMT by processing homeobox protein cut-like1 (CUX1) to produce the physiologically active p110 isoform. In brief, this study revealed that IR-induced EMT as well as migration and invasion of glioma cells are mediated by CTSL through the Akt/GSK-3β/snail and CUX1 pathways. Consequently, this research also led to the identification of a potential novel target for therapeutic intervention of glioma. |
Year of Publication | :
2018
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Journal | :
Cellular signalling
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Date Published | :
2018
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ISSN Number | :
0898-6568
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URL | :
http://linkinghub.elsevier.com/retrieve/pii/S0898-6568(18)30018-4
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DOI | :
10.1016/j.cellsig.2018.01.012
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Short Title | :
Cell Signal
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