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AnnexinA5 promote glioma cell invasion and migration via the PI3K/Akt/NF-κB signaling pathway

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Abstract

As an important member of the Annexins, AnnexinA5 has been attributed important functions in trophoblast membrane repair, anticoagulation and cellular signal transduction. Accumulated studies show that AnnexinA5 is closely associated with various types of carcinomas. However, the potential contribution of AnnexinA5 to glioma cancer progression remains unclear. In this study, we report that AnnexinA5 is significantly upregulated in both high-grade glioma samples and glioma cell lines. Moreover, overexpression of AnnexinA5 promotes cell migration and invasion in vitro and tumorigenicity of glioma cells in nude mice, while knockdown of AnnexinA5 manifests a repressive function during these cellular processes. Importantly, mechanistic studies further reveal that AnnexinA5 is an essential transcriptional target of Snail via activating the PI3K/Akt/NF-κB signaling pathway. Taken together, these findings suggest that AnnexinA5 or the PI3K/Akt/NF-κB pathway may be promising therapeutic molecules to eradicate glioma metastases.

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References

  1. Chhabda S, Carney O, D’Arco F, Jacques TS, Mankad K (2016) The 2016 World Health Organization Classification of tumours of the Central Nervous System: what the paediatric neuroradiologist needs to know. Quant Imaging Med Surg 6:486–489. https://doi.org/10.21037/qims.2016.10.01

    Article  PubMed  PubMed Central  Google Scholar 

  2. Komori T, Sasaki H, Yoshida K (2016) Revised WHO classification of tumours of the central nervous system: summary of the revision and perspective. No shinkei geka Neurol Surg 44:625–635. https://doi.org/10.11477/mf.1436203347

    Article  Google Scholar 

  3. Jansen M, Yip S, Louis DN (2010) Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol 9:717–726. https://doi.org/10.1016/S1474-4422(10)70105-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Rock K, McArdle O, Forde P, Dunne M, Fitzpatrick D, O’Neill B, Faul C (2012) A clinical review of treatment outcomes in glioblastoma multiforme–the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival? Br J Radiol 85:e729-733. https://doi.org/10.1259/bjr/83796755

    Article  Google Scholar 

  5. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109. https://doi.org/10.1007/s00401-007-0243-4

    Article  PubMed  PubMed Central  Google Scholar 

  6. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA 60:166–193. https://doi.org/10.3322/caac.20069

    Article  PubMed  PubMed Central  Google Scholar 

  7. Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA (2001) Malignant glioma: genetics and biology of a grave matter. Genes Dev 15:1311–1333. https://doi.org/10.1101/gad.891601

    Article  PubMed  CAS  Google Scholar 

  8. Gerke V, Moss SE (2002) Annexins: from structure to function. Physiol Rev 82:331–371. https://doi.org/10.1152/physrev.00030.2001

    Article  PubMed  CAS  Google Scholar 

  9. Xue G, Hao LQ, Ding FX, Mei Q, Huang JJ, Fu CG, Yan HL, Sun SH (2009) Expression of annexin a5 is associated with higher tumor stage and poor prognosis in colorectal adenocarcinomas. J Clin Gastroenterol 43:831–837. https://doi.org/10.1097/MCG.0b013e31819cc731

    Article  PubMed  CAS  Google Scholar 

  10. Sun B, Bai Y, Zhang L, Gong L, Qi X, Li H, Wang F, Chi X, Jiang Y, Shao S (2016) Quantitative proteomic profiling the molecular signatures of annexin A5 in lung squamous carcinoma cells. PloS ONE 11:e0163622. https://doi.org/10.1371/journal.pone.0163622

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Lee EK, Cho H, Kim CW (2011) Proteomic analysis of cancer stem cells in human prostate cancer cells. Biochem Biophys Res Commun 412:279–285. https://doi.org/10.1016/j.bbrc.2011.07.083

    Article  PubMed  CAS  Google Scholar 

  12. Martin M, Leffler J, Blom AM (2012) Annexin A2 and A5 serve as new ligands for C1q on apoptotic cells. J Biol Chem 287:33733–33744. https://doi.org/10.1074/jbc.M112.341339

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Li X, Chen L, Liang XJ, Gao YF, Wang XJ, Xu Q, Yan Y, Gao FL (2012) Annexin A5 protein expression is associated with the histological differentiation of uterine cervical squamous cell carcinoma in patients with an increased serum concentration. Mol Med Rep 6:1249–1254. https://doi.org/10.3892/mmr.2012.1078

    Article  PubMed  CAS  Google Scholar 

  14. Rajcevic U, Petersen K, Knol JC, Loos M, Bougnaud S, Klychnikov O, Li KW, Pham TV, Wang J, Miletic H, Peng Z, Bjerkvig R, Jimenez CR, Niclou SP (2009) iTRAQ-based proteomics profiling reveals increased metabolic activity and cellular cross-talk in angiogenic compared with invasive glioblastoma phenotype. Mol Cell Proteomics 8:2595–2612. https://doi.org/10.1074/mcp.M900124-MCP200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Shi X, Zhan L, Xiao C, Lei Z, Yang H, Wang L, Zhao J, Zhang HT (2015) miR-1238 inhibits cell proliferation by targeting LHX2 in non-small cell lung cancer. Oncotarget 6:19043–19054. https://doi.org/10.18632/oncotarget.4232

    Article  PubMed  PubMed Central  Google Scholar 

  16. Duan R, Han L, Wang Q, Wei J, Chen L, Zhang J, Kang C, Wang L (2015) HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-beta pathways. Oncotarget 6:27778–27793. https://doi.org/10.18632/oncotarget.4813

    Article  PubMed  PubMed Central  Google Scholar 

  17. Li W, Zheng J, Deng J, You Y, Wu H, Li N, Lu J, Zhou Y (2014) Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells. Gastroenterology 146:1714–1726 e1715. https://doi.org/10.1053/j.gastro.2014.03.002

    Article  PubMed  CAS  Google Scholar 

  18. Wang J, Zhang Y, Liu X, Ma J, Liu P, Hu C, Zhang G (2014) Annexin A5 inhibits diffuse large B-cell lymphoma cell invasion and chemoresistance through phosphatidylinositol 3-kinase signaling. Oncol Rep 32:2557–2563. https://doi.org/10.3892/or.2014.3547

    Article  PubMed  CAS  Google Scholar 

  19. Wu L, Yang L, Xiong Y, Guo H, Shen X, Cheng Z, Zhang Y, Gao Z, Zhu X (2014) Annexin A5 promotes invasion and chemoresistance to temozolomide in glioblastoma multiforme cells. Tumour Biol 35:12327–12337. https://doi.org/10.1007/s13277-014-2545-1

    Article  PubMed  CAS  Google Scholar 

  20. Singh AR, Joshi S, George E, Durden DL (2014) Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in (12) V-Ha-Ras transgenic mouse glioma model. Cancer Cell Int 14:105. https://doi.org/10.1186/s12935-014-0105-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Shingu T, Yamada K, Hara N, Moritake K, Osago H, Terashima M, Uemura T, Yamasaki T, Tsuchiya M (2003) Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells. Cancer Res 63:4044–4047

    PubMed  CAS  Google Scholar 

  22. Gaelzer MM, Coelho BP, de Quadros AH, Hoppe JB, Terra SR, Guerra MC, Usach V, Guma FC, Goncalves CA, Setton-Avruj P, Battastini AM, Salbego CG (2016) Phosphatidylinositol 3-Kinase/AKT pathway inhibition by doxazosin promotes glioblastoma cells death, upregulation of p53 and triggers low neurotoxicity. PloS ONE 11:e0154612. https://doi.org/10.1371/journal.pone.0154612

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Moss SE, Morgan RO (2004) The annexins. Genome Biol 5:219. https://doi.org/10.1186/gb-2004-5-4-219

    Article  PubMed  PubMed Central  Google Scholar 

  24. Laohavisit A, Davies JM (2011) Annexins. New Phytol 189:40–53. https://doi.org/10.1111/j.1469-8137.2010.03533.x

    Article  PubMed  CAS  Google Scholar 

  25. Mortimer JC, Laohavisit A, Macpherson N, Webb A, Brownlee C, Battey NH, Davies JM (2008) Annexins: multifunctional components of growth and adaptation. J Exp Bot 59:533–544. https://doi.org/10.1093/jxb/erm344

    Article  PubMed  CAS  Google Scholar 

  26. Shin DW, Kwon YJ, Ye DJ, Baek HS, Lee JE, Chun YJ (2016) Auranofin suppresses plasminogen activator inhibitor-2 expression through annexin A5 induction in human prostate cancer cells. Biomol Ther. https://doi.org/10.4062/biomolther.2016.223

    Article  Google Scholar 

  27. Hong M, Park N, Chun YJ (2014) Role of annexin a5 on mitochondria-dependent apoptosis induced by tetramethoxystilbene in human breast cancer cells. Biomol Ther 22:519–524. https://doi.org/10.4062/biomolther.2014.112

    Article  CAS  Google Scholar 

  28. Park N, Chun YJ (2014) Auranofin promotes mitochondrial apoptosis by inducing annexin A5 expression and translocation in human prostate cancer cells. J Toxicol Environ Health A 77:1467–1476. https://doi.org/10.1080/15287394.2014.955834

    Article  PubMed  CAS  Google Scholar 

  29. Tang Y, Lv P, Sun Z, Han L, Luo B, Zhou W (2015) 14-3-3zeta up-regulates hypoxia-inducible factor-1alpha in hepatocellular carcinoma via activation of PI3K/Akt/NF-small ka, CyrillicB signal transduction pathway. Int J Clin Exp Pathol 8:15845–15853

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Shan RF, Zhou YF, Peng AF, Jie ZG (2014) Inhibition of Aurora-B suppresses HepG2 cell invasion and migration via the PI3K/Akt/NF-kappaB signaling pathway in vitro. Exp Ther Med 8:1005–1009. https://doi.org/10.3892/etm.2014.1844

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Rodriguez M, Luo W, Weng J, Zeng L, Yi Z, Siwko S, Liu M (2014) PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-kappaB. Oncogenesis 3:e114. https://doi.org/10.1038/oncsis.2014.29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Felx M, Guyot MC, Isler M, Turcotte RE, Doyon J, Khatib AM, Leclerc S, Moreau A, Moldovan F (2006) Endothelin-1 (ET-1) promotes MMP-2 and MMP-9 induction involving the transcription factor NF-kappaB in human osteosarcoma. Clin Sci 110:645–654. https://doi.org/10.1042/CS20050286

    Article  PubMed  CAS  Google Scholar 

  33. Ahmad A, Biersack B, Li Y, Kong D, Bao B, Schobert R, Padhye SB, Sarkar FH (2013) Targeted regulation of PI3K/Akt/mTOR/NF-kappaB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy. Anti-cancer Agents Med Chem 13:1002–1013

    Article  CAS  Google Scholar 

  34. Zhang LL, Mu GG, Ding QS, Li YX, Shi YB, Dai JF, Yu HG (2015) Phosphatase and tensin homolog (PTEN) represses colon cancer progression through inhibiting paxillin transcription via PI3K/AKT/NF-kappaB pathway. J Biol Chem 290:15018–15029. https://doi.org/10.1074/jbc.M115.641407

    Article  PubMed  CAS  Google Scholar 

  35. Jiao Y, Li H, Liu Y, Guo A, Xu X, Qu X, Wang S, Zhao J, Li Y, Cao Y (2015) Resveratrol inhibits the invasion of glioblastoma-initiating cells via down-regulation of the PI3K/Akt/NF-kappaB signaling pathway. Nutrients 7:4383–4402. https://doi.org/10.3390/nu7064383

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

This work was supported by the National Scientific Foundation of China grants (No. 81560411).

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  1. Chenxing Ji, Hua Guo and Pei Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Chenxing Ji, Hua Guo, Pei Zhang, Wei Kuang, Yanghua Fan & Lei Wu

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  1. Chenxing Ji
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  2. Hua Guo
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Correspondence to Lei Wu.

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Ethical approval

This study was approved by the Review Board at The Second Affiliated Hospital of Nanchang University, and written informed consent was obtained from each participant. All procedures performed were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Ji, C., Guo, H., Zhang, P. et al. AnnexinA5 promote glioma cell invasion and migration via the PI3K/Akt/NF-κB signaling pathway. J Neurooncol 138, 469–478 (2018). https://doi.org/10.1007/s11060-018-2818-4

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  • DOI: https://doi.org/10.1007/s11060-018-2818-4

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