Downregulation of lipolysis‑stimulated lipoprotein receptor promotes cell invasion via claudin‑1‑mediated matrix metalloproteinases in human endometrial cancer

  • Authors:
    • Hiroshi Shimada
    • Seiro Satohisa
    • Takayuki Kohno
    • Takumi Konno
    • Ken‑Ichi Takano
    • Syunta Takahashi
    • Tsubasa Hatakeyama
    • Chihiro Arimoto
    • Tsuyoshi Saito
    • Takashi Kojima
  • View Affiliations

  • Published online on: September 22, 2017     https://doi.org/10.3892/ol.2017.7038
  • Pages:6776-6782
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Abstract

Lipolysis‑stimulated lipoprotein receptor (LSR) is a novel molecule present at tricellular contacts which recruits tricellulin (TRIC), a molecular component of tricellular tight junctions (tTJs). LSR and TRIC are colocalized with the bicellular tight junction (bTJ) protein claudin (CLDN)‑1‑based tight junction strands at tricellular corners. Knockdown of LSR in normal epithelial cells affects tTJ formation and the epithelial barrier function. In cancer cells knockdown of LSR has been demonstrated to increase cell invasion. However, the detailed mechanisms of how the downregulation of LSR enhances cell invasion in cancer remain unclear. In the present study, knockdown of LSR by small interfering RNA (siRNA) in Sawano human endometrial adenocarcinoma cells induced cell invasion. In LSR‑knockdown Sawano cells, upregulation of CLDN‑1 protein, which contributes to the cell invasion via matrix metalloproteinases (MMPs), was observed compared with the control group by western blotting and immunostaining. Knockdown of LSR significantly induced Sp1 transcription factor activity in the CLDN‑1 promoter region. In LSR‑knockdown Sawano cells, DNA microarray analysis demonstrated that MMP‑1, MMP‑2 and MMP‑10 mRNA levels were increased, and the protein levels of membrane‑type 1‑MMP, MMP‑2, MMP‑9 and MMP‑10 were shown to be increased on western blots. Knockdown of CLDN‑1 with siRNA prevented the upregulation of cell invasion induced by the knockdown of LSR in Sawano cells. On the invasive front of human endometrial carcinoma tissue samples, a decrease in LSR and increase in CLDN‑1 protein levels were observed using immunohistochemical methods. In conclusion, the results indicate that the downregulation of LSR promotes cell invasion of human endometrial cancer via CLDN‑1 mediation of MMPs. This mechanism is important for studying the association of tTJs with the cellular invasion of cancer.

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Shimada, H., Satohisa, S., Kohno, T., Konno, T., Takano, K., Takahashi, S. ... Kojima, T. (2017). Downregulation of lipolysis‑stimulated lipoprotein receptor promotes cell invasion via claudin‑1‑mediated matrix metalloproteinases in human endometrial cancer. Oncology Letters, 14, 6776-6782. https://doi.org/10.3892/ol.2017.7038
MLA
Shimada, H., Satohisa, S., Kohno, T., Konno, T., Takano, K., Takahashi, S., Hatakeyama, T., Arimoto, C., Saito, T., Kojima, T."Downregulation of lipolysis‑stimulated lipoprotein receptor promotes cell invasion via claudin‑1‑mediated matrix metalloproteinases in human endometrial cancer". Oncology Letters 14.6 (2017): 6776-6782.
Chicago
Shimada, H., Satohisa, S., Kohno, T., Konno, T., Takano, K., Takahashi, S., Hatakeyama, T., Arimoto, C., Saito, T., Kojima, T."Downregulation of lipolysis‑stimulated lipoprotein receptor promotes cell invasion via claudin‑1‑mediated matrix metalloproteinases in human endometrial cancer". Oncology Letters 14, no. 6 (2017): 6776-6782. https://doi.org/10.3892/ol.2017.7038