Skip to main content

Advertisement

Log in

RETRACTED ARTICLE: Nucleolin Promotes TGF-β Signaling Initiation via TGF-β Receptor I in Glioblastoma

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

This article was retracted on 15 June 2017

Abstract

The transforming growth factor β (TGF-β) pathway plays a key role in oncogenesis of advanced cancers, involving the non-Smad and Smad pathways. Meanwhile, nucleolin on the cell surface has been also reported to affect activation of signaling pathways. However, the effect of cell surface nucleolin on TGF-β pathway in glioblastoma is not still understood. Here, using antibodies of nucleolin and TGF-β receptor I (TβR-I), we observed blocking of either nucleolin or TβR-I inhibited the phosphorylation of CrkL, Erk1/2, and Smad2. Using nucleolin siRNA, nucleolin knockdown was also identified to suppress the expression of p-CrkL, p-Erk1/2, and p-Smad2. Furthermore, immunoprecipitation revealed the interaction between cell surface nucleolin and TβR-I on the U87 cell membrane. In addition, U87 cell wound-healing, soft-agar and MTT assay also showed si-nucleolin could obviously impair wound closure (p < 0.001), colony formation (p < 0.001) and cell growth (p < 0.001). In conclusion, nucleolin promotes and regulates the TGF-β pathway by interacting with TβR-I and is required for initiation and activation of TGF-β signaling. Thus, nucleolin could be a key factor in glioblastoma pathogenesis and considered a therapeutic target, which may also mediate more signaling pathways.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alete DE, Weeks ME, Hovanession AG, Hawadle M, Stoker AW (2006) Cell surface nucleolin on developing muscle is a potential ligand for the axonal receptor protein tyrosine phosphatase-sigma. FEBS J 273:4668–4681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birmpas C, Briand JP, Courty J, Katsoris P (2012) The pseudopeptide HB-19 binds to cell surface nucleolin and inhibits angiogenesis. Vasc Cell 4:21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandra M, Zang S, Li H, Zimmerman LJ, Champer J, Tsuyada A, Chow A, Zhou W, Yu Y, Gao H, Ren X, Lin RJ, Wang SE (2012) Nuclear translocation of type I transforming growth factor β receptor confers a novel function in RNA processing. Mol Cell Biol 32:2183–2195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davies M, Robinson M, Smith E, Huntley S, Prime S, Paterson I (2005) Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways. J Cell Biochem 95:918–931

    Article  CAS  PubMed  Google Scholar 

  • Drabsch Y, ten Dijke P (2012) TGF-β signalling and its role in cancer progression and metastasis. Cancer Metastasis Rev 31:553–568

    Article  CAS  PubMed  Google Scholar 

  • Farin K, Di Segni A, Mor A, Pinkas-Kramarski R (2009) Structure-function analysis of nucleolin and ErbB receptors interactions. PLoS ONE 4:e6128

    Article  PubMed  PubMed Central  Google Scholar 

  • Ginisty H, Sicard H, Roger B, Bouvet P (1999) Structure and functions of nucleolin. J Cell Sci 112:761–772

    CAS  PubMed  Google Scholar 

  • Hill CS (2009) Nucleocytoplasmic shuttling of Smad proteins. Cell Res 19:36–46

    Article  CAS  PubMed  Google Scholar 

  • Katsuno Y, Lamouille S, Derynck R (2013) TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol 25:76–84

    Article  CAS  PubMed  Google Scholar 

  • Kjellman C, Olofsson SP, Hansson O, Von Schantz T, Lindvall M, Nilsson I, Salford LG, Sjogren HO, Widegren B (2000) Expression of TGF-beta isoforms, TGF-beta receptors, and SMAD molecules at different stages of human glioma. Int J Cancer 89:251–258

    Article  CAS  PubMed  Google Scholar 

  • Krust B, El Khoury D, Nondier I, Soundaramourty C, Hovanessian AG (2011) Targeting surface nucleolin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the malignant tumor cell type. BMC Cancer 11:333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li AG, Wang D, Feng XH, Wang XJ (2004) Latent TGFβ1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J 23:1770–1781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM Jr, Ivanova MM, Bates PJ, Appana SN, Datta S, Kulesza P, McBryan J, Young LS, Klinge CM (2012) Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells. PLoS ONE 7:e38278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv S, Qin J, Yi R, Coreman M, Shi R, Kang H, Yao C (2013) CrkL efficiently mediates cell proliferation, migration, and invasion induced by TGF-β pathway in glioblastoma. J Mol Neurosci 51:1046–1051

    Article  CAS  PubMed  Google Scholar 

  • Massague J, Seoane J, Wotton D (2005) Smad transcription factors. Genes Dev 19:2783–2810

    Article  CAS  PubMed  Google Scholar 

  • Matsuura I, Denissova NG, Wang G, He D, Long J, Liu F (2004) Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 430:226–231

    Article  CAS  PubMed  Google Scholar 

  • Pickup M, Novitskiy S, Moses HL (2013) The roles of TGF-β in the tumour microenvironment. Nat Rev Cancer 13:788–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reyes-Reyes EM, Akiyama SK (2008) Cell-surface nucleolin is a signal transducing P-selectin binding protein for human colon carcinoma cells. Exp Cell Res 1314:2212–2223

    Article  Google Scholar 

  • Shi Y, Massague J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700

    Article  CAS  PubMed  Google Scholar 

  • Song N, Ding Y, Zhuo W, He T, Fu Z, Chen Y, Song X, Fu Y, Luo Y (2012) The nuclear translocation of endostatin is mediated by its receptor nucleolin in endothelial cells. Angiogenesis 15:697–711

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Liu SZ, Lin Y, Cao XP, Liu JM (2014) TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways. Biochem Biophys Res Commun 443:1066–1072

    Article  CAS  PubMed  Google Scholar 

  • Tague SE, Muralidharan V, Souza-Schorey CD (2004) ADP-ribosylation factor 6 regulates tumor cell invasion through the activation of the MEK/ERK signaling pathway. Proc Natl Acad Sci U S A 101:9671–9676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turck N, Lefebvre O, Gross I, Gendry P, Kedinger M, Simon-Assmann P, Launay JF (2006) Effect of laminin-1 on intestinal cell differentiation involves inhibition of nuclear nucleolin. J Cell Physiol 206:545–555

    Article  CAS  PubMed  Google Scholar 

  • Vehlow A, Cordes N (2013) Invasion as target for therapy of glioblastoma multiforme. Biochim Biophys Acta 1836:236–244

    CAS  PubMed  Google Scholar 

  • Weiss A, Attisano L (2013) The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol 2:47–63

    Article  CAS  PubMed  Google Scholar 

  • Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by National Key Basic Research Program of China (No. 2013CB932502), and National Natural Science Foundation of China (No. 81171295). We greatly thank Shigang Zhao in Sandy lab for valuable suggestions and writing.

Conflict of Interest

The authors state that there are no conflicts of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chengjun Yao.

Additional information

Shunzeng Lv and Jie Zhang contributed equally to this work.

An erratum to this article is available at http://dx.doi.org/10.1007/s12031-017-0935-8.

This article has been retracted at the request of Dr Chengjun Yao, Dr. Dongxiao Zhuang, The Editor in Chief and the Publisher per the Committee on Publication Ethics guidelines for the following reasons:

– There is strong reason to believe that the peer review process was compromised

– The article shows evidence of irregularities in authorship during the submission process

– Dr. Chengjun Yao has confirmed that he was not involved in the submission process and does not support its publication

– Dr. Dongxiao Zhuang has confirmed that he was not involved in the research nor in the writing of this article

– The National Natural Science Foundation of China mentioned in this paper was not involved in the research reported in this article

About this article

Cite this article

Lv, S., Zhang, J., Han, M. et al. RETRACTED ARTICLE: Nucleolin Promotes TGF-β Signaling Initiation via TGF-β Receptor I in Glioblastoma. J Mol Neurosci 55, 1–6 (2015). https://doi.org/10.1007/s12031-014-0292-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-014-0292-9

Keywords

Navigation