Skip to main content
SpringerLink
Log in

TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Targeting protein for Xklp2 (TPX2) is a microtubule-associated protein involved in targeting the motor protein Xklp2 to microtubules. TPX2 overexpression plays a key role in the progression of human cancers. But the underlying mechanism remains unclear.

Aims

This study aimed to investigate the effects and mechanisms of TPX2 on the cell cycle, apoptosis, and epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma (HCC).

Methods

The tissue TPX2 mRNA and protein were assessed by quantitative reverse transcriptase PCR and immunoblot. Cell proliferation, cell cycle, apoptosis, and invasion were determined by CCK-8, FACS, TdT-UTP nick end-labeling, and transwell assays. Immunoblotting was performed to detect the expression of target proteins.

Results

TPX2 was highly expressed in tumor tissues compared with non-tumoral tissues, and TPX2 overexpression was positively correlated with poor prognosis. Knockdown TPX2 effectively reduced cell growth, G2/M arrest, induced apoptosis and cell death, and inhibited EMT. Mechanistically, in the TPX2-siRNA-treated groups, cell-cycle-related proteins cyclin A1, cyclin B1, cyclin E1, and cdk4 were up-regulated, while cyclin D1, cdk2, and p21 proteins were down-regulated. Cell-apoptosis-related proteins Bax, p53, caspase-3, and caspase-8 levels were increased. EMT-related proteins E-cadherin was up-regulated, while N-cadherin, β-catenin, MMP-9, MMP-2, and Slug were down-regulated. We also found that knockdown TPX2 in HCC cell lines caused a significant decrease in the level of p-Akt and p-ERK which are important signaling pathways in tumor formation.

Conclusions

TPX2 expression is associated with proliferation, apoptosis, and EMT in hepatocellular carcinoma cell and patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Cha C, Fong Y, Jarnagin WR, et al. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg. 2003;197:753–758.

    Article  PubMed  Google Scholar 

  3. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–1255.

    Article  PubMed  Google Scholar 

  4. Shah SA, Cleary SP, Wei AC, et al. Recurrence after liver resection for hepatocellular carcinoma : risk factors, treatment, and outcomes. Surgery. 2007;141:330–339.

    Article  PubMed  Google Scholar 

  5. Sumie S, Kuromatsu R, Okuda K, et al. Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol. 2008;15:1375–1382.

    Article  PubMed  Google Scholar 

  6. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329–340.

    Article  CAS  PubMed  Google Scholar 

  7. Warner SL, Stephens BJ, Nwokenkwo S, et al. Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells. Clin Cancer Res. 2009;15:6519–6528.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Villanueva A, Newell P, Chiang DY, et al. Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis. 2007;27:55–76.

    Article  CAS  PubMed  Google Scholar 

  9. Pang A, Ng IO, Fan ST, et al. Clinicopathologic significance of genetic alterations in hepatocellular carcinoma. Cancer Genet Cytogenet. 2003;146:8–15.

    Article  CAS  PubMed  Google Scholar 

  10. Wong N, Lai P, Pang E, et al. Genomic aberrations in human hepatocellular carcinomas of differing etiologies. Clin Cancer Res. 2000;6:4000–4009.

    CAS  PubMed  Google Scholar 

  11. de Castro P, Malumbres M. Mitotic stress and chromosomal instability in cancer: the case for TPX2. Genes Cancer. 2012;3:721–730.

    Article  Google Scholar 

  12. Neumayer G, Belzil C, Gruss OJ, et al. TPX2: of spindle assembly, DNA damage response, and cancer. Cell Mol Life Sci. 2014;71:3027–3047.

    Article  CAS  PubMed  Google Scholar 

  13. Ma Y, Lin D, Sun W, et al. Expression of targeting protein for xklp2 associated with both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer. Clin Cancer Res. 2006;12:1121–1127.

    Article  CAS  PubMed  Google Scholar 

  14. Chang H, Wang J, Tian Y, et al. The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer. Oncol Rep. 2012;27:1353–1359.

    CAS  PubMed  Google Scholar 

  15. Yan L, Li S, Xu C, et al. Target protein for Xklp2 (TPX2), a microtubule-related protein, contributes to malignant phenotype in bladder carcinoma. Tumour Biol. 2013;34:4089–4100.

    Article  CAS  PubMed  Google Scholar 

  16. Hsu PK, Chen HY, Yeh YC, et al. TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma. J Gastroenterol. 2013;49:1231–1240.

    Article  PubMed  Google Scholar 

  17. Huang Y, Guo W, Kan H. TPX2 is a prognostic marker and contributes to growth and metastasis of human hepatocellular carcinoma. Int J Mol Sci. 2014;15:18148–18161.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Lu X, Zhao H, Yang H, et al. A prospective clinical study on early recurrence of hepatocellular carcinoma after hepatectomy. J Surg Oncol. 2009;100:488–493.

    Article  PubMed  Google Scholar 

  19. Sun YF, Xu Y, Yang XR, et al. Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection. Hepatology. 2013;57:1458–1468.

    Article  CAS  PubMed  Google Scholar 

  20. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442.

    Article  CAS  PubMed  Google Scholar 

  21. Bruix J, Boix L, Sala M, et al. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–219.

    Article  CAS  PubMed  Google Scholar 

  22. Wei P, Zhang N, Xu Y, et al. TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer. J Transl Med. 2013;11:313.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Meng X, Franklin DA, Dong J, et al. MDM2-p53 pathway in hepatocellular carcinoma. Cancer Res. 2014;74:7161–7167.

    Article  CAS  PubMed  Google Scholar 

  24. Lee SC, Tan HT, Chung MC. Prognostic biomarkers for prediction of recurrence of hepatocellular carcinoma: current status and future prospects. World J Gastroenterol. 2014;20:3112–3124.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Bogachek MV, De Andrade JP, Weigel RJ. Regulation of epithelial–mesenchymal transition through SUMOylation of transcription factors. Cancer Res. 2015;75:11–15.

    Article  CAS  PubMed  Google Scholar 

  26. Saunders LR, McClay DR. Sub-circuits of a gene regulatory network control a developmental epithelial–mesenchymal transition. Development. 2014;141:1503–1513.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Rogers CD, Jayasena CS, Nie S, et al. Neural crest specification: tissues, signals, and transcription factors. Wiley Interdiscip Rev Dev Biol. 2012;1:52–68.

    Article  CAS  PubMed  Google Scholar 

  28. Yang H, He L, Kruk P, et al. Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells. Int J Cancer. 2006;119:2304–2312.

    Article  CAS  PubMed  Google Scholar 

  29. Morgan-Lappe SE, Tucker LA, Huang X, et al. Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res. 2007;67:4390–4398.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Guangdong Natural Science Foundation (2013B022000069).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People’s Republic of China

    Bo Liang, Yu Huang, Hua He, Jialu Li, Hui Liao, Xiao Liu, Xincheng Liu & Dinghua Yang

  2. Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, Guangdong Province, People’s Republic of China

    Chunhong Jia & Xiaochun Bai

  3. Department of General Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China

    Bo Liang

Authors
  1. Bo Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunhong Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hua He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jialu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hui Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xincheng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaochun Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dinghua Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dinghua Yang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liang, B., Jia, C., Huang, Y. et al. TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT. Dig Dis Sci 60, 2360–2372 (2015). https://doi.org/10.1007/s10620-015-3730-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3730-9

Keywords

Search

Navigation