OncoTargets and Therapy (Mar 2023)
Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel
Abstract
Jiaru Hu,1 Qing He,1 Tian Tian,2 Na Chang,3 Liting Qian1 1Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China; 2Department of Respiratory Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230001, People’s Republic of China; 3Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230001, People’s Republic of ChinaCorrespondence: Liting Qian, Email [email protected]: 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
