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Lectin PCL inhibits the Warburg effect of PC3 cells by combining with EGFR and inhibiting HK2

  • Authors:
    • Hong Zhang
    • Xia Du
    • Ting-Ting Sun
    • Chun-Liu Wang
    • Ye Li
    • Shou-Zhen Wu

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  • Published online on: January 16, 2017     https://doi.org/10.3892/or.2017.5367
  • Pages: 1765-1771
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Abstract

Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production. The expression of HK2 is closely related to epidermal growth factor receptor (EGFR) and downstream signaling pathway activation, therefore, we investigated the interaction of PCL with EGFR by western blot analysis and found that PCL could suppress the binding of epidermal growth factor (EGF) with EGFR and HK2 expression. Also, we explored the binding mechanism between the PCL and EGFR through molecular docking and molecular dynamics simulations and found that PCL bocked the active site of EGFR which is also the binding site of the nature ligand EGF, the resulting conformation has higher stability than EGF in complex with EGFR. The results indicated that PCL could competitively bind to EGFR binding pocket and then prevent EGF from binding to EGFR, blocking the autophosphorylation of the EGFR tyrosine kinase, after that the EGFR activation is inhibited. Collectively, our studies concluded that PCL inhibits tumor cell glycolysis by combining with EGFR and reducing HK2 expression.
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March-2017
Volume 37 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 3.8
  • Ranked Oncology
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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Zhang H, Du X, Sun T, Wang C, Li Y and Wu S: Lectin PCL inhibits the Warburg effect of PC3 cells by combining with EGFR and inhibiting HK2. Oncol Rep 37: 1765-1771, 2017.
APA
Zhang, H., Du, X., Sun, T., Wang, C., Li, Y., & Wu, S. (2017). Lectin PCL inhibits the Warburg effect of PC3 cells by combining with EGFR and inhibiting HK2. Oncology Reports, 37, 1765-1771. https://doi.org/10.3892/or.2017.5367
MLA
Zhang, H., Du, X., Sun, T., Wang, C., Li, Y., Wu, S."Lectin PCL inhibits the Warburg effect of PC3 cells by combining with EGFR and inhibiting HK2". Oncology Reports 37.3 (2017): 1765-1771.
Chicago
Zhang, H., Du, X., Sun, T., Wang, C., Li, Y., Wu, S."Lectin PCL inhibits the Warburg effect of PC3 cells by combining with EGFR and inhibiting HK2". Oncology Reports 37, no. 3 (2017): 1765-1771. https://doi.org/10.3892/or.2017.5367