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外泌体 TPX2 的传递促进 NSCLC 细胞对多西紫杉醇的转移和耐药
Authors Hu J , He Q, Tian T, Chang N, Qian L
Received 14 December 2022
Accepted for publication 16 March 2023
Published 27 March 2023 Volume 2023:16 Pages 197—210
DOI https://doi.org/10.2147/OTT.S401454
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Background: Lung cancer, most of which is non-small cell lung cancer (NSCLC), is the most common tumor in the world, and drug resistance, as a major problem in clinical treatment, has attracted extensive attention. However, the role and mechanism of Targeting protein for Xenopus kinesin-like protein 2 (TPX2), which is highly expressed in NSCLC, is still unclear.
Methods: Bioinformatics analysis was used to analyze the relationship between TPX2 and the clinicopathological features of NSCLC. Stable TPX2 overexpression cell lines with were constructed by lentivirus infection, and the effect of TPX2 on proliferation, migration, invasion and chemoresistance to docetaxel was characterized by the CCK8, wound healing, transwell, colony formation assay and FACS. An in vivo lung homing mouse model was used to further confirmed the role of TPX2 on metastasis. Exosomes were extracted by differential centrifugation from the culture supernatant, and their functions were investigated by co-culture with tumor cells. Gene expression was detected via Western blot and real time PCR (RT-qPCR).
Results: Overexpression of TPX2 was related to the poor prognosis of NSCLC. Promoted migration, invasion and metastasis, and reduced the sensitivity of NSCLC cells to docetaxel. The abundance of TPX2 can be packaged in vesicles and transported to other cells. In addition, overexpression of TPX2 induced the accumulation of β-catenin and C-myc.
Conclusion: Our findings indicated that intercellular transfer of exosomal TPX2 triggered metastasis and resistance against to docetaxel in lung cancer cells, through activating downstream WNT/β-catenin signaling pathway.
Keywords: metastasis, docetaxel, TPX2, exosome, NSCLC