Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel

Abstract

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

Data Sharing Statement

The analyzed datasets for this study can be found in the TCGA (https://portal.gdc.cancer.gov).

Acknowledgments

We thank Yan Hua, Qiyi Yi and Lei Lv on guiding experimental techniques and the staff who participated in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This research was funded by the Youth Fund of Anhui Cancer Hospital (grant number 2020YJQN005), the Hefei Science and Technology Bureau Fund (grant number J2020Y01) and the Fundamental Research Funds for the Central Universities (grant number WK9110000188).