Research on The Membrane Surface Nucleolin Participated The Activation of Epidermal Growth Factor Receptor Signaling_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANG Xiangshan ¹ , FAN Kaixi ² , LI Chengjun ³ , LI Aiping ⁴ , ZHANG Jing ¹ , FENG Man. ¹

1.Department of Pathology， Affiliated Hospital of Shandong Academy of Medical Sciences， Jinan 250031， Shandong Province， China;;
2.Center Laboratory， Affiliated Hospital of Shandong Academy of Medical Sciences， Jinan 250031， Shandong Province，China;;
3.Department of General Surgery， Affiliated Hospital of Shandong Academy of Medical Sciences， Jinan 250031，Shandong Province， China;;

Corresponding author：

YANG Xiangshan, Email: yangxiangshan163@163.com

Keywords：

Membrane surface nucleolin; Epidermal growth factor receptor; Activation of signaling

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To explore the effect of membrane surface nucleolin （NCL） on activation of epidermal growth factor receptor （EGFR） signaling.
Methods 　Immunohistochemistry was used to identify the expressions of membrane surface NCL or EGFR in pallilary thyroid carcinoma （PTC） tissues. The level of phosphorlated EGFR in TPC-1 cells was observed by Western blot. TPC-1 cells invasion capacity was detected by Transwell assay.
Results 　The posi-tive expression rates of membrane surface NCL and EGFR in PTC tissues were 100% （56/56） and 80.4% （45/56） respe-ctively， while the expressions of NCL and EGFR were related with lymph node metastasis （P＜0.05）. There was posi-tive correlation between the expressions of NCL and EGFR （r=0.635， P＜0.01）. Western blot showed that anti-NCL or anti-EGFR of TPC-1 cells could inhibit the expression of phosphorlation EGFR （P＜0.01）. Transwell assay showed the number of membrane-invading cells were reduced significantly in anti-NCL group anti-EGFR group （P＜0.01）.
Conclusions 　Membrane surface NCL may be a kind of indispensable component in activation of EGFR signaling， by which EGFR can participate in growth and invasion of tumors. NCL can be used as a target for developing a new field of tumor treatment.

Citation： YANG Xiangshan,FAN Kaixi,LI Chengjun,LI Aiping,ZHANG Jing,FENG Man.. Research on The Membrane Surface Nucleolin Participated The Activation of Epidermal Growth Factor Receptor Signaling. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(10): 1117-1121. doi: Copy

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20.	Qu WS， Tian DS， Guo ZB， et al. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the assoc-iated secondary damage in rats after spinal cord injury[J]. J Neur-oinflammation， 2012， 9：178.
21.	王晓艳，沈守荣，刘芬结，等. 结肠癌中NGX6抑制EGFR/K-ras/JNK/c-Jun/cyclin D1信号通路的研究[J]. 生物化学与生物物理进展， 2008， 35(5)：570-576.
22.	Chen CH， Wang SW， Chen CW， et al. MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endom-etrial cancer[J]. Gynecol Oncol， 2013， 128(3)：560-567.
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24.	Li C， Zhang X， Cheng L， et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice[J]. Cancer Gene Ther， 2013， 20(2)：101-108.
25.	Heuckmann JM， Rauh D， Thomas RK. Epidermal growth factor receptor(EGFR) signaling and covalent EGFR inhibition in lung cancer[J]. J Clin Oncol， 2012， 30(27)：3417-3420.
26.	Yang W， Xia Y， Cao Y， et al. EGFR-induced and PKCε monou-biquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis[J]. Mol Cell， 2012， 48(5)：771-784.
27.	， 286(51)：43816-43829.

1. Tajrishi MM， Tuteja R， Tuteja N. Nucleolin：The most abundantmultifunctional phosphoprotein of nucleolus[J]. Commun Integr Biol， 2011， 4(3)：267-275.
2. Ginisty H， Sicard H， Roger B， et al. Structure and functions of nucleolin[J]. J Cell Sci， 1999， 112(Pt6)：761-772.
3. Orrick LR， Olson MO， Busch H. Comparison of nucleolar prot-eins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis[J]. Proc Natl Acad Sci USA， 1973， 70(5)：1316-1320.
4. Kobayashi J， Fujimoto H， Sato J， et al. Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway[J]. PLoS One， 2012， 7(11)：e49245.
5. Wang SA， Li HY， Hsu TI， et al. Heat shock protein 90 stabilizesnucleolin to increase mRNA stability in mitosis[J]. J Biol Chem，.
6. Ding Y， Song N， Liu C， et al. Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin[J]. Arterioscler Thromb Vasc Biol， 2012， 32(9)：e126-e134.
7. Iliakis G， Krieg T， Guan J， et al. Evidence for an S-phase checkpoint regulating DNA replication after heat shock：a review[J]. Int J Hyperthermia， 2004， 20(2)：240-249.
8. Xu Z， Joshi N， Agarwal A， et al. Knocking down nucleolin expr-ession in gliomas inhibits tumor growth and induces cell cycle arrest[J]. J Neurooncol， 2012， 108(1)：59-67.
9. 王慷慨，肖献忠. 核仁素在细胞增殖与细胞凋亡中的作用[J]. 中南大学学报：医学版， 2004， 29(6)：707-710.
10. Peng L， Liang J， Wang H， et al. High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stageⅡpancreatic ductal adenocarcinoma[J]. Clin Cancer Res， 2010， 16(14)：3734-3742.
11. 蒙国照，肖胜军，曾思恩，等. 细胞表面核仁素表达下调抑制肝癌细胞生长[J]. 中华肿瘤学杂志， 2011， 33(1)：23-27.
12. 田晓彩，刘先领，胡春宏. 核仁素表达下调对阿霉素所致乳腺癌细胞增殖抑制和凋亡的影响[J]. 中华肿瘤杂志， 2010， 32(4)：271-272.
13. Huang Y， Shi H， Zhou H， et al. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin[J]. Blood， 2006， 107(9)：3564-3571.
14. Christian S， Pilch J， Akerman ME， et al. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels[J]. J Cell Biol， 2003， 163(4)：871-878.
15. Reyes-Reyes EM， Akiyama SK. Cell surface nucleolin is a signal transducing P-selectin binding protein for human colon carcin cells[J]. Exp Cell Res， 2008， 314(11-12)：2212-2223.
16. Turck N， Lefebvre O， Gross I， et al. Effect of laminin-1 on inte-stinal cell differentiation involves inhibition of nuclear nucleolin[J]. J Cell Physiol， 2006， 206(2)：545-555.
17. Harms G， Kraft R， Grelle G， et al. Identification of nucleolin as a new L-selectin ligand[J]. Biochem J， 2001， 360(Pt 3)：531-538.
18. Krust B， El Khoury D， Nondier I， et al. Targeting surface nucle-olin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the malignanttumor cell type[J]. BMC Cancer， 2011， 11：333.
19. Joo EJ， Yang H， Park Y， et al. Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma[J]. Cell Biochem， 2010， 110(5)：1272-1278.
20. Qu WS， Tian DS， Guo ZB， et al. Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the assoc-iated secondary damage in rats after spinal cord injury[J]. J Neur-oinflammation， 2012， 9：178.
21. 王晓艳，沈守荣，刘芬结，等. 结肠癌中NGX6抑制EGFR/K-ras/JNK/c-Jun/cyclin D1信号通路的研究[J]. 生物化学与生物物理进展， 2008， 35(5)：570-576.
22. Chen CH， Wang SW， Chen CW， et al. MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endom-etrial cancer[J]. Gynecol Oncol， 2013， 128(3)：560-567.
23. Kobayashi K， Hagiwara K. Epidermal growth factor receptor(EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer(NSCLC)[J]. Target Oncol， 2013， 8(1)：27-33.
24. Li C， Zhang X， Cheng L， et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice[J]. Cancer Gene Ther， 2013， 20(2)：101-108.
25. Heuckmann JM， Rauh D， Thomas RK. Epidermal growth factor receptor(EGFR) signaling and covalent EGFR inhibition in lung cancer[J]. J Clin Oncol， 2012， 30(27)：3417-3420.
26. Yang W， Xia Y， Cao Y， et al. EGFR-induced and PKCε monou-biquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis[J]. Mol Cell， 2012， 48(5)：771-784.
27. ， 286(51)：43816-43829.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research on The Membrane Surface Nucleolin Participated The Activation of Epidermal Growth Factor Receptor Signaling

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