Ionizing Radiation Increases Axl Protein Degradation in A549 Lung Adenocarcinoma Cells through an Autophagolysosomal Pathway
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Axl receptor tyrosine kinase (Axl) plays multiple roles in the tumorigenesis and metastasis of severalcancers. Herein, we report that the degradation of Axl protein following ionizing radiation (IR) exposure is associatedwith the autophagolysosomal pathway in A549 lung adenocarcinoma cells. The level of Axl protein was markedlydecreased after IR exposure to 5 or 10 Gy, although the Axl transcriptional level remained unaltered. IR-mediatedAxl degradation was inhibited by the lysosomal inhibitor, chloroquine, whereas treatment with the proteasomeinhibitors, MG132 and lactacystin, did not affect Axl degradation. Furthermore, the expression of Axl was correlatedwith increased cleavage of GFP-LC3-Ⅰ to GFP-LC3-Ⅱ (specific protein markers of autophagy) in IR treated cellscompared to non-IR treated cells from 1-48 h after IR. Moreover, Axl co-localized with GFP-LC3 fusion protein inpunctate spots, which are well-characterized markers of autophagosome formation, indicating that the IR-induceddegradation of Axl protein is mediated by the autophagic process. Thus, our findings suggest that IR increases thedegradation of Axl protein through the autophagolysosomal pathway and promotes the growth arrest of non-smallcell lung cancer (NSCLC) cells.
Abstract
Axl receptor tyrosine kinase (Axl) plays multiple roles in the tumorigenesis and metastasis of severalcancers. Herein, we report that the degradation of Axl protein following ionizing radiation (IR) exposure is associatedwith the autophagolysosomal pathway in A549 lung adenocarcinoma cells. The level of Axl protein was markedlydecreased after IR exposure to 5 or 10 Gy, although the Axl transcriptional level remained unaltered. IR-mediatedAxl degradation was inhibited by the lysosomal inhibitor, chloroquine, whereas treatment with the proteasomeinhibitors, MG132 and lactacystin, did not affect Axl degradation. Furthermore, the expression of Axl was correlatedwith increased cleavage of GFP-LC3-Ⅰ to GFP-LC3-Ⅱ (specific protein markers of autophagy) in IR treated cellscompared to non-IR treated cells from 1-48 h after IR. Moreover, Axl co-localized with GFP-LC3 fusion protein inpunctate spots, which are well-characterized markers of autophagosome formation, indicating that the IR-induceddegradation of Axl protein is mediated by the autophagic process. Thus, our findings suggest that IR increases thedegradation of Axl protein through the autophagolysosomal pathway and promotes the growth arrest of non-smallcell lung cancer (NSCLC) cells.