Skip to main content
Erschienen in: Tumor Biology 1/2016

10.08.2015 | Original Article

Involvement of nuclear protein C23 in activation of EGFR signaling in cervical cancer

verfasst von: Junyuan Yan, Yanling Zhang, Cuili Ren, Wenshuang Shi, Lijun Chen

Erschienen in: Tumor Biology | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

Nuclear protein C23 and epidermal growth factor receptor (EGFR) are reported to be correlated with cervical cancer (CC). However the correlations between C23 and EGFR were rarely reported. Here, this study explored the effects of C23 in activation of EGFR signaling pathway. In our study, immunohistochemistry was used to identify the expression of C23 or EGFR in CC tissues. The level of the phosphorylated EGFR was observed by western blot, and cell invasion capacity was detected by Transwell assay. In this study, we found that C23 and EGFR were highly expressed in cervical cancer tissues, while C23 on the cell surface mainly expressed in CC tissues with lymph node metastasis, and was correlated to EGFR statistically. In vitro, western blot showed that either anti-C23 or anti-EGFR antibodies can inhibit the phosphorlation of EGFR with significant differences (p < 0.01). Besides, based on Transwell assay, the number of membrane-invading cells was reduced significantly in anti-C23 group, and no significant difference was found compared with anti-EGFR treatment (p > 0.05). In conclusion, C23 on the cell surface may be a kind of indispensable component in activation of EGFR signaling, by which C23 can participate in the growth and invasion of tumors. C23 antagonists may provide a new field for cervical cancer therapy.
Literatur
1.
Zurück zum Zitat Andersen JS, Lam YW, Leung AKL, Ong S, Lyon CE, Lamond AI, et al. Nucleolar proteome dynamics. Nature. 2005;433:77–83.CrossRefPubMed Andersen JS, Lam YW, Leung AKL, Ong S, Lyon CE, Lamond AI, et al. Nucleolar proteome dynamics. Nature. 2005;433:77–83.CrossRefPubMed
2.
Zurück zum Zitat Andersen JS, Wilkinson CJ, Mayor T, Mortensen P, Nigg EA, Mann M. Proteomic characterization of the human centrosome by protein correlation profiling. Nature. 2003;426:570–4.CrossRefPubMed Andersen JS, Wilkinson CJ, Mayor T, Mortensen P, Nigg EA, Mann M. Proteomic characterization of the human centrosome by protein correlation profiling. Nature. 2003;426:570–4.CrossRefPubMed
3.
Zurück zum Zitat Bicknell K, Brooks G, Kaiser P, Chen H, Dove BK, Hiscox JA. Nucleolin is regulated both at the level of transcription and translation. Biochem Biophys Res Comm. 2005;332:817–22.CrossRefPubMed Bicknell K, Brooks G, Kaiser P, Chen H, Dove BK, Hiscox JA. Nucleolin is regulated both at the level of transcription and translation. Biochem Biophys Res Comm. 2005;332:817–22.CrossRefPubMed
4.
Zurück zum Zitat Prestayko AW, Klomp GR, Schmoll DJ, Busch H. Comparison of proteins of ribosomal subunits and nucleolar preribosomal particles from Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Biochemistry. 1974;13:1945–51.CrossRefPubMed Prestayko AW, Klomp GR, Schmoll DJ, Busch H. Comparison of proteins of ribosomal subunits and nucleolar preribosomal particles from Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Biochemistry. 1974;13:1945–51.CrossRefPubMed
5.
Zurück zum Zitat Bugler B, Caizergues-Ferrer M, Bouche G, Bourbon H, Amalric F. Detection and localization of a class of proteins immunologically related to a 100 KDa nucleolar protein. Eur J Biochem. 1982;128:473–80. Bugler B, Caizergues-Ferrer M, Bouche G, Bourbon H, Amalric F. Detection and localization of a class of proteins immunologically related to a 100 KDa nucleolar protein. Eur J Biochem. 1982;128:473–80.
6.
Zurück zum Zitat Srivastava M, McBride OW, Fleming PJ, Pollard HB, Burns AL. Genomic organization and chromosomal localization of the human nucleolin gene. J Biol Chem. 1990;265:14922–31.PubMed Srivastava M, McBride OW, Fleming PJ, Pollard HB, Burns AL. Genomic organization and chromosomal localization of the human nucleolin gene. J Biol Chem. 1990;265:14922–31.PubMed
7.
Zurück zum Zitat Lischwe MA, Roberts KD, Yeoman LC, Busch H. Nucleolar specific acidic phosphoprotein C23 is highly methylated. J Biol Chem. 1982;257:14600–2.PubMed Lischwe MA, Roberts KD, Yeoman LC, Busch H. Nucleolar specific acidic phosphoprotein C23 is highly methylated. J Biol Chem. 1982;257:14600–2.PubMed
8.
Zurück zum Zitat Ginisty H, Sicard H, Roger B, Bouvet P. Structure and functions of nucleolin. J Cell Sci. 1999;112:761–72.PubMed Ginisty H, Sicard H, Roger B, Bouvet P. Structure and functions of nucleolin. J Cell Sci. 1999;112:761–72.PubMed
9.
Zurück zum Zitat Máximo V, Rios E, Sobrinho-Simões M. Oncocytic lesions of the thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands. Int J Surg Pathol. 2014;22:33–6.CrossRefPubMed Máximo V, Rios E, Sobrinho-Simões M. Oncocytic lesions of the thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands. Int J Surg Pathol. 2014;22:33–6.CrossRefPubMed
10.
Zurück zum Zitat Masago K, Asato R, Fujita S, Hirano S, Tamura Y, Kanda T, et al. Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma. Int J Cancer. 2009;124:2744–9.CrossRefPubMed Masago K, Asato R, Fujita S, Hirano S, Tamura Y, Kanda T, et al. Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma. Int J Cancer. 2009;124:2744–9.CrossRefPubMed
11.
Zurück zum Zitat Kobayashi J, Fujimoto H, Sato J, Hayashi I, Burma S, Matsuura S, et al. Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway. PLoS One. 2012;7, e49245.CrossRefPubMedPubMedCentral Kobayashi J, Fujimoto H, Sato J, Hayashi I, Burma S, Matsuura S, et al. Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway. PLoS One. 2012;7, e49245.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Wang SA, Li HY, Hsu TI, Chen SH, Wu CJ, Chang WC, et al. Heat shock protein 90 stabilizes nucleolin to increase mRNA stability in mitosis. J Biol Chem. 2011;286:43816–29.CrossRefPubMedPubMedCentral Wang SA, Li HY, Hsu TI, Chen SH, Wu CJ, Chang WC, et al. Heat shock protein 90 stabilizes nucleolin to increase mRNA stability in mitosis. J Biol Chem. 2011;286:43816–29.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Ding Y, Song N, Liu C, He T, Zhuo W, He X, et al. Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin. Arterioscler Thromb Vasc Biol. 2012;32:e126–34.CrossRefPubMed Ding Y, Song N, Liu C, He T, Zhuo W, He X, et al. Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin. Arterioscler Thromb Vasc Biol. 2012;32:e126–34.CrossRefPubMed
14.
Zurück zum Zitat Iliakis G, Krieg T, Guan J, Wang Y, Leeper D. Evidence for an S-phase checkpoint regulating DNA replication after heat shock: a review. Int J Hyperthermia. 2004;20:240–9.CrossRefPubMed Iliakis G, Krieg T, Guan J, Wang Y, Leeper D. Evidence for an S-phase checkpoint regulating DNA replication after heat shock: a review. Int J Hyperthermia. 2004;20:240–9.CrossRefPubMed
15.
Zurück zum Zitat Xu Z, Joshi N, Agarwal A, Dahiya S, Bittner P, Smith E, et al. Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest. J Neurooncol. 2012;108:59–67.CrossRefPubMed Xu Z, Joshi N, Agarwal A, Dahiya S, Bittner P, Smith E, et al. Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest. J Neurooncol. 2012;108:59–67.CrossRefPubMed
16.
Zurück zum Zitat Peng L, Liang J, Wang H, Song X, Rashid A, Gomez HF, et al. High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stage II pancreatic ductal adenocarcinoma. Clin Cancer Res. 2010;16:3734–42.CrossRefPubMed Peng L, Liang J, Wang H, Song X, Rashid A, Gomez HF, et al. High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stage II pancreatic ductal adenocarcinoma. Clin Cancer Res. 2010;16:3734–42.CrossRefPubMed
17.
Zurück zum Zitat Huang Y, Shi H, Zhou H, Song X, Yuan S, Luo Y. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood. 2006;107:3564–71.CrossRefPubMed Huang Y, Shi H, Zhou H, Song X, Yuan S, Luo Y. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood. 2006;107:3564–71.CrossRefPubMed
18.
Zurück zum Zitat Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol. 2003;163:871–8.CrossRefPubMedPubMedCentral Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol. 2003;163:871–8.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Reyes-Reyes EM, Akiyama SK. Cell surface nucleolin is a signal transducing P-selectin binding protein for human colon carcin cells. Exp Cell Res. 2008;314:2212–23.CrossRefPubMedPubMedCentral Reyes-Reyes EM, Akiyama SK. Cell surface nucleolin is a signal transducing P-selectin binding protein for human colon carcin cells. Exp Cell Res. 2008;314:2212–23.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Turck N, Lefebvre O, Gross I, Gendry P, Kedinger M, Simon-Assmann P, et al. Effect of laminin-1 on intestinal cell differentiation involves inhibition of nuclear nucleolin. J Cell Physiol. 2006;206:545–5.CrossRefPubMed Turck N, Lefebvre O, Gross I, Gendry P, Kedinger M, Simon-Assmann P, et al. Effect of laminin-1 on intestinal cell differentiation involves inhibition of nuclear nucleolin. J Cell Physiol. 2006;206:545–5.CrossRefPubMed
21.
22.
Zurück zum Zitat Krust B, El Khoury D, Nondier I, Soundaramourty C, Hovanessian AG. 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. 2011;11:333.CrossRefPubMedPubMedCentral Krust B, El Khoury D, Nondier I, Soundaramourty C, Hovanessian AG. 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. 2011;11:333.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Joo EJ, Yang H, Park Y, Park NY, Toida T, Linhardt RJ, et al. Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma. Cell Biochem. 2010;110:1272–8.CrossRef Joo EJ, Yang H, Park Y, Park NY, Toida T, Linhardt RJ, et al. Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma. Cell Biochem. 2010;110:1272–8.CrossRef
24.
Zurück zum Zitat Zhang C, Zhu H, Yang X, Lou J, Zhu D, Lu W, et al. P53 and p38 MAPK pathways are involved in MONCPT-induced cell cycle G2/M arrest in human non-small cell lung cancer A549. J Cancer Res Clin Oncol. 2010;136:437–45.CrossRefPubMed Zhang C, Zhu H, Yang X, Lou J, Zhu D, Lu W, et al. P53 and p38 MAPK pathways are involved in MONCPT-induced cell cycle G2/M arrest in human non-small cell lung cancer A549. J Cancer Res Clin Oncol. 2010;136:437–45.CrossRefPubMed
25.
Zurück zum Zitat Qu WS, Tian DS, Guo ZB, Fang J, Zhang Q, Yu ZY, et al. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury. J Neuroinflammation. 2012;9:178.CrossRefPubMedPubMedCentral Qu WS, Tian DS, Guo ZB, Fang J, Zhang Q, Yu ZY, et al. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury. J Neuroinflammation. 2012;9:178.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Chen CH, Wang SW, Chen CW, Huang MR, Hung JS, Huang HC, et al. MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer. Gynecol Oncol. 2013;128:560–7.CrossRefPubMed Chen CH, Wang SW, Chen CW, Huang MR, Hung JS, Huang HC, et al. MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer. Gynecol Oncol. 2013;128:560–7.CrossRefPubMed
27.
Zurück zum Zitat Kobayashi K, Hagiwara K. Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC). Target Oncol. 2013;8:27–33.CrossRefPubMedPubMedCentral Kobayashi K, Hagiwara K. Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC). Target Oncol. 2013;8:27–33.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Li C, Zhang X, Cheng L, Dai L, Xu F, Zhang J, et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice. Cancer Gene Ther. 2013;20:101–8.CrossRefPubMed Li C, Zhang X, Cheng L, Dai L, Xu F, Zhang J, et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice. Cancer Gene Ther. 2013;20:101–8.CrossRefPubMed
29.
Zurück zum Zitat Heuckmann JM, Rauh D, Thomas RK. Epidermal growth factor receptor (EGFR) signaling and covalent EGFR inhibition in lung cancer. J Clin Oncol. 2012;30:3417–20.CrossRefPubMed Heuckmann JM, Rauh D, Thomas RK. Epidermal growth factor receptor (EGFR) signaling and covalent EGFR inhibition in lung cancer. J Clin Oncol. 2012;30:3417–20.CrossRefPubMed
30.
Zurück zum Zitat Yang W, Xia Y, Cao Y, Zheng Y, Bu W, Zhang L, et al. EGFR-induced and PKCs monoubiquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis. Mol Cell. 2012;48:771–84.CrossRefPubMedPubMedCentral Yang W, Xia Y, Cao Y, Zheng Y, Bu W, Zhang L, et al. EGFR-induced and PKCs monoubiquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis. Mol Cell. 2012;48:771–84.CrossRefPubMedPubMedCentral
Metadaten
Titel
Involvement of nuclear protein C23 in activation of EGFR signaling in cervical cancer
verfasst von
Junyuan Yan
Yanling Zhang
Cuili Ren
Wenshuang Shi
Lijun Chen
Publikationsdatum
10.08.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 1/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3889-x

Weitere Artikel der Ausgabe 1/2016

Tumor Biology 1/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.