期刊
CANCER LETTERS
卷 509, 期 -, 页码 89-104出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.03.028
关键词
AURKA; Cytotoxic autophagy; CXCL5; NSCLC; Radiosensitivity
类别
资金
- National Natural Science Foundation of China [81672977, 81703032]
The study found that AURKA is upregulated in NSCLC and is associated with poor prognosis, and that silencing AURKA can increase radiosensitivity and reduce migration and invasion ability. CXCL5 is identified as a key downstream effector of AURKA, and the AURKA-CXCL5 axis and autophagy play important roles in regulating NSCLC cells' sensitivity to radiotherapy.
Aurora kinase A (AURKA) regulates apoptosis and autophagy in various diseases and has shown promising clinical effects. Nevertheless, the complex regulatory mechanism of AURKA and autophagy in non-small-cell lung cancer (NSCLC) radiosensitivity remains to be elucidated. Here, we showed that AURKA was upregulated in NSCLC cell lines and tissues and that AURKA overexpression was significantly related to a poor prognosis, tumor stage and lymph node metastasis in NSCLC. Interestingly, AURKA expression was significantly increased after 8Gy radiotherapy. Silencing of AURKA enhanced radiosensitivity and impaired migration and invasion in vivo and in vitro. Mechanistically, we determined that CXCL5, a member of the chemokine family, was a key downstream effector of AURKA, and the phenotype induced by AURKA silencing was partly due to CXCL5 inhibition. We further demonstrated that the AURKA-CXCL5 axis played an essential role in NSCLC autophagy and that the activation of cytotoxic autophagy attenuated the malignant biological behavior of NSCLC cells mediated by AURKA-CXCL5. In general, we revealed the role of the AURKA-CXCL5 axis and autophagy in regulating the sensitivity of NSCLC cells to radiotherapy, which may provide potential therapeutic targets and new strategies for combatting NSCLC resistance to radiotherapy.
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